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Zhenlei Wang,1 Zengci Run,1 Huamin Wang,2 Xiaojun He,3 Jian Li1 1Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China; 2Department of Pediatrics, Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 3School of Ophthalmology & Optometry School of Biomedical Engineering Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of ChinaCorrespondence: Jian Li, Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Jinshui District, Zhengzhou, Henan, 450008, People’s Republic of China, Tel +86 18638927768, Email garfycat@126.com Xiaojun He, School of Ophthalmology & Optometry School of Biomedical Engineering Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 15626166187, Email 513080867@qq.comPurpose: The search for effective and low-risk treatment methods for colorectal cancer (CRC) is a pressing concern, given the inherent risks and adverse reactions associated with traditional therapies. Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment, offering advantages such as non-radiation, non-invasiveness, and targeted treatment. Consequently, the development of nanoparticles with high stability, biocompatibility, and photothermal effects has become a significant research focus within the field of PTT.Methods: In this study, TiO2-Ti3C2 nanocomposites were synthesized and characterized, and their photothermal conversion efficiency in the near-infrared region II (NIR-II) was determined. Then studied the in vivo and in vitro photothermal activity and anti-tumor effect of TiO2-Ti3C2 in human colorectal cancer cell lines and nude mice subcutaneous tumor model.Results: The results showed t

Hui Feng,1 Yang Yue,1 Yan Zhang,1 Jingqi Liang,1 Liang Liu,1 Qiong Wang,1 Qian Feng,2 Hongmou Zhao1 1Department of Foot and Ankle Surgery, Honghui Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi, 710054, People’s Republic of China; 2Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of ChinaCorrespondence: Hongmou Zhao, Department of Foot and Ankle Surgery, Honghui Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi, 710054, People’s Republic of China, Email zhaohongmou@xiyi.edu.cn Qian Feng, Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China, Email qianfeng@cqu.edu.cnAbstract: Tissue engineering holds great potential for tissue repair and rejuvenation. Plant-derived exosome-like nanoparticles (ELNs) have recently emerged as a promising avenue in tissue engineering. However, there is an urgent need to understand how plant ELNs can be therapeutically applied in clinical disease management, especially for tissue regeneration. In this review, we comprehensively examine the properties, characteristics, and isolation techniques of plant ELNs. We also discuss their impact on the immune system, compatibility with the human body, and their role in tissue regeneration. To ensure the suitability of plant ELNs for tissue engineering, we explore various engineering and modification strategies. Additionally, we provide insights into the progress of commercialization and industrial perspectives on plant ELNs. This review aims to highlight the potential of plant ELNs in regenerative medicine by exploring the current research landscape and key findings.Keywords: plant, exosome-like nanoparticles, nanomedicine, tissue engineering, cartilage, wound, bone

Ting Li,1,* Lianshan Guo,2,* Jiaxu Li,3,* Xingyu Mu,4 Lijuan Liu,1 Shulin Song,1 Ningbin Luo,1 Qi Zhang,5 Bin Zheng,1 Guanqiao Jin1 1Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 3Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Graduate School, Nanning Normal University, Nanning, 530001, People’s Republic of China; 4Department of Nuclear Medicine, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 5Laboratory Animal Center, Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanqiao Jin, Email jinguanqiao77@gxmu.edu.cnBackground: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance.Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of U

Jing-Jing Huang,1,* Lin Jia,2,3,* Qiao-Jun Zhang,4 Hao-Hong Li,5 Da-Li Zheng,2 Ming Zheng3 1Second Department of Dental Implant, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Fujian Key Laboratory of Oral Diseases, Fujian Biological Materials Engineering and Technology Center of Stomatology, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, 350004, People’s Republic of China; 3Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 4Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361000, People’s Republic of China; 5College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Zheng, Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Middle Road, Fuzhou, 350001, People’s Republic of China, Tel +86-591-83736431, Email zmdentist@163.com Da-Li Zheng, Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, People’s Republic of China, Tel +86-591-83720599, Email dalizheng@fjmu.edu.cnPurpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)’s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry.Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens’ values for surface roughness, microhardness, and flexural strength (MPa) were measured after i

Chenqi Chang,1 Heng Liu,2 Xiaotong Li,2 Dandan Song,1 Yue Liu,1 Chang Lu,1 Yu Zhen,1 Ying Chen,1 Jinguo Xu,1 Weidong Li,1 Xiaobin Jia,3 Zhipeng Chen,1 Rui Chen1 1School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, 671003, People’s Republic of China; 3School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of ChinaCorrespondence: Rui Chen; Zhipeng Chen, Email chenrui@njucm.edu.cn; czpcpu2000@hotmail.comIntroduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties.Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo.Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage.Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have

Abebayehu N Yilma,1,2,* Rajnish Sahu,1,* Praseetha Subbarayan,1,* Francois Villinger,3 Mamie T Coats,4 Shree R Singh,1 Vida A Dennis1 1Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA; 2Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA; 3Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, USA; 4Department of Clinical and Diagnostics Sciences, School of Health Professionals, The University at Alabama at Birmingham (UAB), Birmingham, AL, USA*These authors contributed equally to this workCorrespondence: Vida A Dennis, Center for NanoBiotechnology Research (CNBR), Alabama State University, 1627 Harris Way, Montgomery, AL, USA, Tel +1 334-604-9205, Email vdennis@alasu.eduIntroduction: Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need.Methods: Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV–visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and

Werner EG Müller, Meik Neufurth, Shunfeng Wang, Heinz C Schröder, Xiaohong Wang ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, GermanyCorrespondence: Werner EG Müller; Xiaohong Wang, ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, Mainz, D-55128, Germany, Tel +49 6131 392 5791, Email wmueller@uni-mainz.de; wang013@uni-mainz.deAbstract: There is a need for novel nanomaterials with properties not yet exploited in regenerative nanomedicine. Based on lessons learned from the oldest metazoan phylum, sponges, it has been recognized that two previously ignored or insufficiently recognized principles play an essential role in tissue regeneration, including biomineral formation/repair and wound healing. Firstly, the dependence on enzymes as a driving force and secondly, the availability of metabolic energy. The discovery of enzymatic synthesis and regenerative activity of amorphous biosilica that builds the mineral skeleton of siliceous sponges formed the basis for the development of successful strategies for the treatment of osteochondral impairments in humans. In addition, the elucidation of the functional significance of a second regeneratively active inorganic material, namely inorganic polyphosphate (polyP) and its amorphous nanoparticles, present from sponges to humans, has pushed forward the development of innovative materials for both soft (skin, cartilage) and hard tissue (bone) repair. This energy-rich molecule exhibits a property not shown by any other biopolymer: the delivery of metabolic energy, even extracellularly, necessary for the ATP-dependent tissue regeneration. This review summarizes the latest developments in nanobiomaterials based on these two evolutionarily old, regeneratively active materials, amorphous silica

Ariff Haikal Hairil Anuar,1 Siti Aisyah Abd Ghafar,1 Rohazila Mohamad Hanafiah,1 Vuanghao Lim,2 Nur Farah Atiqah Mohd Pazli1 1Department of Basic Sciences, Faculty of Dentistry, Universiti Sains Islam Malaysia, Kuala Lumpur, 55100, Malaysia; 2Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, 13200, MalaysiaCorrespondence: Siti Aisyah Abd Ghafar, Department of Basic Sciences, Faculty of Dentistry, Universiti Sains Islam Malaysia, Level 18, Tower B, Persiaran MPAJ, Jalan Pandan Utama, Kuala Lumpur, 55100, Malaysia, Tel +60389471157, Fax +60389472566, Email aisyahghafar@usim.edu.myIntroduction: This study aimed to characterize silver nanoparticles-kaempferol (AgNP-K) and its antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Green synthesis method was used to synthesize AgNP-K under the influence of temperature and different ratios of silver nitrate (AgNO3 and kaempferol).Methods: AgNP-K 1:1 was synthesized with 1 mM kaempferol, whereas AgNP-K 1:2 with 2 mM kaempferol. The characterization of AgNP-K 1:1 and AgNP-K 1:2 was performed using UV–visible spectroscopy (UV–Vis), Zetasizer, transmission electron microscopy (TEM), scanning electron microscopy-dispersive X-ray spectrometer (SEM-EDX), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. The antibacterial activities of five samples (AgNP-K 1:1, AgNP-K 1:2, commercial AgNPs, kaempferol, and vancomycin) at different concentrations (1.25, 2.5, 5, and 10 mg/mL) against MRSA were determined via disc diffusion assay (DDA), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) assay, and time-kill assay.Results: The presence of a dark brown colour in the solution indicated the formation of AgNP-K. The UV–visible absorption spectrum of the synthesized AgNP-K exhibited a broad peak at 447 nm. TEM, Zetasizer, and SEM-EDX results showed that the morphology and size of A

Yi He,1,2 Lejia Zhang,1,2 Siyuan Huang,1,2 Yuquan Tang,3 Yiming Li,1,2 Hongyu Li,1,2 Guanhui Chen,4 Xun Chen,1,2 Xiliu Zhang,1,2 Wei Zhao,1,2 Feilong Deng,1,2 Dongsheng Yu1,2 1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 3Zhujiang Hospital, Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Department of Stomatology, the Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, 518107, People’s Republic of ChinaCorrespondence: Feilong Deng; Dongsheng Yu, Email dengfl@mail.sysu.edu.cn; yudsh@mail.sysu.edu.cnBackground: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used

Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of

Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed Abdul Kareem Saeed Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Ahmed Mohsen Elsaid Hamdan,6 Mohamed Mansour Khalifa,7 Sandra Hababeh,8 Mohammad Ahmad Khasawneh,9 Gehad M Khamis,10 Jakline Nelson,11 Passant M Mohie,10 Rania A Gad,12 Amira Rizk,13 Soad L Kabil,14 Mohamed Kandeel El-Ashery,15,16 Bhaskara R Jasti,17 Nahla A Elzohairy,18,19 Tayseer Elnawawy,20 Fatma E Hassan,21,22 Mohamed A El- Nabarawi23 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 7Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 8Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 9Department of Chemistry, College of Science U.A.E. University, Al-Ain, United Arab Emirates; 10Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 11Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 12Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 13Food Science and Technology Department, Faculty of Agricultural, Tanta University, Tanta, Egypt; 14Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 15Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 16Medicinal Chemistry Department, Faculty of Pharmac

Putu Yuliandari, Masri Sembiring Maha, Novaria Sari Dewi Panjaitan Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong Science Center, Bogor, WJ, IndonesiaCorrespondence: Novaria Sari Dewi Panjaitan, Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Jl. Raya Bogor No. 490, Cibinong – Bogor Km. 46, Bogor, WJ, Indonesia, Email nova014@brin.go.id

Na Qi,1,* Xiantai Zhou,2,* Ningzhu Ma,2 Jianguo Zhang,2 Zhenlin Wang,2 Xin Zhang,1 Aimin Li1 1Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China; 2Department of Pharmacy, Guilin Medical University, Guilin, 541004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aimin Li; Xin Zhang, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China, Email liaimin2005@163.com; 252089553@qq.comIntroduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvβ 3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects.Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice.Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytoto

Shailey Gale Twamley,1– 3 Niclas Gimber,4 Héctor Eduardo Sánchez-Ibarra,1,2 Tobias Christaller,1,2 Victoria Isakzai,1,2 Harald Kratz,5 Ronodeep Mitra,6 Lena Kampen,1– 3 Anke Stach,1,2 Heike Heilmann,7 Berit Söhl-Kielczynski,8 Eno Essien Ebong,6,9,10 Jan Schmoranzer,4 Agnieszka Münster-Wandowski,7,* Antje Ludwig1– 3,* 1Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany; 2Department of Cardiology, Angiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; 3DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; 4Advanced Medical Bioimaging Core Facility (AMBIO), Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 5Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 7Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 8Institute for Integrative Neurophysiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 9Department of Bioengineering, Northeastern University, Boston, MA, USA; 10Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA*These authors contributed equally to this workCorrespondence: Shailey Gale Twamley; Antje Ludwig, Tel +49-30-450-528455 ; +49-30-450-513196, Fax +49-30-450-528922 ; +49-30-450941, Email shailey.tw

Vinith Yathindranath,1,2 Nura Safa,1,2 Mateusz Marek Tomczyk,1,3 Vernon Dolinsky,1,3 Donald W Miller1,2 1Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada; 2PrairieNeuro Research Centre, Health Science Centre, Winnipeg, MB, Canada; 3Children’s Hospital Research Institute Manitoba, Health Science Centre, Winnipeg, MB, CanadaCorrespondence: Donald W Miller, Tel +1 204 789 3278, Email donald.miller@umanitoba.caPurpose: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lingering threat to public health has fueled the search for effective therapeutics to treat SARS-CoV-2. This study aimed to develop lipid nanoparticle (LNP) inhibitors of SARS-CoV-2 entry to reduce viral infection in the nose and upper airway.Methods: Two types of LNP formulations were prepared following a microfluidic mixing method. The LNP-Trap consisted of DOPC, DSPC, cholesterol, and DSPE-PEG-COOH modified with various spike protein binding ligands, including ACE2 peptide, recombinant human ACE2 (rhACE2) or monoclonal antibody to spike protein (mAb). The LNP-Trim consisted of ionizing cationic DLin-MC3-DMA, DSPC, cholesterol, and DMG-PEG lipids encapsulating siACE2 or siTMPRSS2. Both formulations were assayed for biocompatibility and cell uptake in airway epithelial cells (Calu-3). Functional assessment of activity was performed using SARS-CoV-2 spike protein binding assays (LNP-Trap), host receptor knockdown (LNP-Trim), and SARS-CoV-2 pseudovirus neutralization assay (LNP-Trap and LNP-Trim). Localization and tissue distribution of fluorescently labeled LNP formulations were assessed in mice following intranasal administration.Results: Both LNP formulations were biocompatible based on cell impedance and MTT cytotoxicity studies in Calu-3 cells at concentrations as high as 1 mg/mL. LNP-Trap formulations were able to bind spike protein and inhibit pseudovirus infection by 90% in Calu-3 cells. LNP-Trim formulations

Ernest Moles,1– 4 David W Chang,1– 3 Friederike M Mansfeld,1– 3 Alastair Duly,1,2 Kathleen Kimpton,1 Amy Logan,1– 4 Christopher B Howard,5 Kristofer J Thurecht,5,6 Maria Kavallaris1– 4 1Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, 2052, Australia; 2UNSW Australian Centre for Nanomedicine, Faculty of Engineering, UNSW, Sydney, NSW, 2052, Australia; 3School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, NSW, 2052, Australia; 4UNSW RNA Institute, Faculty of Science, UNSW, Sydney, NSW, 2052, Australia; 5Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, QLD, 4072, Australia; 6Centre for Advanced Imaging, ARC Training Centre for Innovation in Biomedical Imaging Technologies, University of Queensland, St Lucia, QLD, 4072, AustraliaCorrespondence: Ernest Moles; Maria Kavallaris, Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, 2052, Australia, Email emoles@ccia.org.au; m.kavallaris@ccia.unsw.edu.auIntroduction: Despite improvements in chemotherapy and molecularly targeted therapies, the life expectancy of patients with advanced non-small cell lung cancer (NSCLC) remains less than 1 year. There is thus a major global need to advance new treatment strategies that are more effective for NSCLC. Drug delivery using liposomal particles has shown success at improving the biodistribution and bioavailability of chemotherapy. Nevertheless, liposomal drugs lack selectivity for the cancer cells and have a limited ability to penetrate the tumor site, which severely limits their therapeutic potential. Epidermal growth factor receptor (EGFR) is overexpressed in NSCLC tumors in about 80% of patients, thus representing a promising NSCLC-specific target for redirecting liposome-embedded chemotherapy to the tumor site.Methods: Herein, we investigated the targeting of PEGylated liposomal doxorubicin (Caelyx), a powerful off-the-shelf antitumo

Chuihao Kong,1,2,* Kaidi Wang,1,2,* Lei Sun,1,3 Hongsu Zhao,1,2 Tongsheng Wang,1 Wuxi Zhou,1 Deling Wu,1,2 Fengqing Xu1,2 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China; 3Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wuxi Zhou; Fengqing Xu, School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan District, Hefei, 230012, People’s Republic of China, Email zhouwuxi@ahtcm.edu.cn; xufengqing@ahtcm.edu.cnBackground: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics.Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo.Results: The results indicated that MC-CDs with a uniform spherical particle size of 1– 5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in n

Malarmugila Manimaran,1,* Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,* Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia*These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email ccchang01@nycu.edu.tw; lvkiew@um.edu.myIntrod

Huang Y, Chen Y, Cheng G, et al. Int J Nanomedicine. 2024;19:231–245. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 5C on page 240 is incorrect. The correct Figure 5 is as follows. Figure 5 Continued. Figure 5 Results of in vitro cytocompatibility testing. (A) CCK-8 assay and (B) cell viability on hydrogels after 1, 3 and 5 days of culture. (C) Images of live/dead staining of cells following incubation on hydrogels. (D) Images taken using a confocal laser scanning microscope (CLSM) show HUVECs stained with rhodamine-coupled phalloidin (red) and DAPI (blue) after three days of growth. A one-way ANOVA was used to determine statistical significance: *p < 0.05, **p < 0.01. The authors apologise for this error.

Ding P, Jin Q, Chen X, et al. Int J Nanomedicine. 2019;14:7533-7548. At the author’s request, we, the Editor and Publisher of the journal International Journal of Nanomedicine have retracted the following article. During a recent review of the article, the authors identified an error in the use of the transmission electron microscopy (TEM) images for Figure 2A, which could potentially confuse readers. After discussing this issue with the editorial team and providing the original data, the authors agreed that the potential confusion could not be adequately addressed through simple correction. Although the results of TEM were independent of the in vivo and in vitro experiments and did not affect the effectiveness of the nanovaccines in the study, they could have compromised the accuracy and reliability of the findings. The authors apologize for the errors in the article and appreciate the readership’s understanding in this matter. However, the authors remain confident in the results and conclusions of this study and with the original material well preserved, hope to submit a revised version of the article for republication following reevaluation. The journal has acknowledged this. In the meantime, in the interest of upholding research integrity and ensuring the trustworthiness of the scientific record, the authors believe that it is necessary to retract the article. We, the Editor and Publisher, understand and agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yu-Chi Tu,&ast; Yu-Mei Wang,&ast; Li-Jun Yao Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Jun Yao, Email ljyao@hust.edu.cnAbstract: DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy.Keywords: macrophages, DNA nanomaterials, therapy, macrophage-related diseases

Donghyuk Kim, Hyunjung Kim Department of Mechanical Engineering, Ajou University, Suwon-si, Gyeonggi-do, 16499, KoreaCorrespondence: Hyunjung Kim, Email hyunkim@ajou.ac.krIntroduction: Due to its distinct advantage of non-invasive application in treatment, photothermal therapy (PTT) is being studied by many researchers to reduce the need for surgical incisions. It is characterized by the injection of nanoparticles into biological tissue as photothermal agents (PTAs) which diffuse within the tissue. In this study, the diffusion behavior of various doses of gold nanoparticles (AuNPs) injected into tumor tissues is analyzed and the effectiveness of PTT at each elapsed time after injection is confirmed by numerical analysis.Methods: The diffusion behavior of AuNPs within biological tissues is assessed using the convection-diffusion equation, while the temperature distribution is determined using the Pennes bioheat transfer equation. In addition, the effect of the diffusion behavior of AuNPs on the effectiveness of PTT is quantitatively confirmed by analyzing the temperature distribution in the medium through the apoptotic variable. Numerical simulation parameters are selected with doses ranging from 100 to 400 μg/mL, elapsed time after injection from 1 min to 24 h, and laser power ranging from 0 to 1 W.Results: After evaluating PTT’s efficacy in every situation, it was discovered that a dosage of 100– 300 μg/mL produced the best therapeutic result, with the highest impact occurring 12 hours after injection. In contrast, when the dosage was 400 μg/mL, the highest therapeutic effect was achieved after 18 hours post-injection. Additionally, it was discovered that the ideal laser power at each injection dose was 0.22, 0.14, 0.12, and 0.12 W, respectively.Conclusion: The conditions required to achieve the optimal treatment effect at each dosage, presented here, are expected to accelerate the commercialization of PTT.Keywords: apoptosis, elapsed time after injection, g

Yanyi Wang,1,2,&ast; Juan Wen,1– 3,&ast; Tong Lu,1,2 Wei Han,2,4 Kai Jiao,5 Huang Li1,2 1Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia; 4Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 5Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Han, Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Email doctorhanwei@hotmail.com Huang Li, Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Tel +86-25-83620173, Fax +86-25-83620200, Email lihuang76@nju.edu.cnAbstract: Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs bu

Tao Jiang,1,2 Weijian Chen,3 Chao Lu,1,2 Jiyong Yang,3 Ziquan Zeng,1,2 Wenqiang Li,4 Hongsheng Liu,5 Nana Huang,5 Yuhui Chen,6 Wengang Liu1,2 1Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 2Department of Orthopedics, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 3The Fifth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, School of Sport and Health, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 5Guangdong Huayan Biomedical Science and Technology Center, Guangzhou, 511441, People’s Republic of China; 6Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Hengfu Road 60, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email liuwengang74@163.com Yuhui Chen, Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China, Email ah1990726@163.comBackground: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bac

Qiu Huang,&ast; Yue Ge,&ast; Yu He, Jian Wu, Yonghua Tong, Haojie Shang, Xiao Liu, Xiaozhuo Ba, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Chen; Kun Tang, Email zhqchen8366@163.com; tangsk1990@163.comAbstract: Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.Keywords: nanoparticles, cancer therapy, cancer-associated fibroblasts, drug delivery

Shengshan Ma,1,2,&ast; Suyang Zheng,1,&ast; Dong Li,3 Wenhao Hu,4 Liming Wang1 1Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Sports Medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China; 3Department of Trauma Center, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 4Department of Orthopedic Surgery, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Wang, Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86-25-5227-1000, Fax +86-25-5226-9924, Email wlmnjsy@163.comPurpose: This study aims to explore a novel scaffold for osteotendinous junction regeneration and to preliminarily verify its osteogenic and tenogenic abilities in vitro.Methods: A polycaprolactone (PCL) scaffold with aligned and orthogonal fibers was created using melt electrowriting (MEW) and fused deposition modeling (FDM). The scaffold was coated with Type I collagen, and hydroxyapatite was carefully added to separate the regions intended for bone and tendon regeneration, before being rolled into a cylindrical shape. Human adipose-derived stem cells (hADSCs) were seeded to evaluate viability and differentiation. Scaffold characterization was performed with Scanning Electron Microscope (SEM). Osteogenesis was assessed by alkaline phosphatase (ALP) and Alizarin red staining, while immunostaining and transcription-quantitative polymerase chain reaction (RT-qPCR) evaluated osteogenic and tendogenic markers.Results: Scaffolds were developed in four variations: aligned (A), collagen-coated aligne

Liyang Dong,1,&ast; Yafang Zhao,1,&ast; Juan Luo,1,2 Xiaopeng Li,1 Shuxian Wang,1 Menghan Li,1 Peng Zou,1 Hui Kong,1 Qingguo Wang,1 Yan Zhao,1 Huihua Qu1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingguo Wang; Yan Zhao, Email wangqg8558@sina.com; zhaoyandr@163.comBackground: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases.Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats.Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate

Ailin Zou,1,&ast; Tingting Xiao,1,&ast; Boyu Chi,1,2 Yu Wang,1 Lipeng Mao,1,2 Dabei Cai,1,2 Qingqing Gu,1 Qianwen Chen,1 Qingjie Wang,1 Yuan Ji,1 Ling Sun1,2 1Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Changzhou Clinical Medical College, Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Sun; Qingjie Wang, Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China, Email sunling85125@hotmail.com; wang-qingjie@hotmail.comBackground: Cardiac repair remains a thorny issue for survivors of acute myocardial infarction (AMI), due to the regenerative inertia of myocardial cells. Cell-free therapies, such as exosome transplantation, have become a potential strategy for myocardial injury. The aim of this study was to investigate the role of engineered exosomes in overexpressing Growth Differentiation Factor-15 (GDF-15) (GDF15-EVs) after myocardial injury, and their molecular mechanisms in cardiac repair.Methods: H9C2 cells were transfected with GDF-15 lentivirus or negative control. The exosomes secreted from H9C2 cells were collected and identified. The cellular apoptosis and autophagy of H2O2-injured H9C2 cells were assessed by Western blotting, TUNEL assay, electron microscopy, CCK-8 and caspase 3/7 assay. A rat model of AMI was constructed by ligating the left anterior descending artery. The anti-apoptotic, pro-angiogenic effects of GDF15-EVs treatment, as well as ensuing functional and histological recovery were evaluated. Then, mRNA sequencing was performed to identify the differentially expressed mRNAs after GDF15-EVs treatment.Results: GDF15-EVs inhibited apoptosis and promoted autophagy in H2O2 injured H9C2 cells. GDF15-EVs effectively decrea

Vesna Spasovski,1,2,&ast; Anna Romolo,1,3,&ast; Urška Zagorc,4 Vesna Arrigler,4 Matic Kisovec,5 Apolonija Bedina Zavec,5 Matev&zcaron; Arko,1 Adrienn Molnár,6,7 Gitta Schlosser,7 Aleš Igli&ccaron;,3,8 Ksenija Kogej,4 Veronika Kralj-Igli&ccaron;1 1University of Ljubljana, Faculty of Health Sciences, Laboratory of Clinical Biophysics, Ljubljana, Slovenia; 2Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia; 3University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Physics, Ljubljana, Slovenia; 4University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia; 5National Institute of Chemistry, Department of Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia; 6Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary; 7MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Faculty of Science, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary; 8University of Ljubljana, Faculty of Medicine, Laboratory of Clinical Biophysics, Ljubljana, Slovenia&ast;These authors contributed equally to this workCorrespondence: Veronika Kralj-Igli&ccaron;, Email veronika.kralj-iglic@zf.uni-lj.siIntroduction: Lipid nanovesicles associated with bioactive phytochemicals from spruce needle homogenate (here called nano-sized hybridosomes or nanohybridosomes, NSHs) were considered.Methods: We formed NSHs by mixing appropriate amounts of lecithin, glycerol and supernatant of isolation of extracellular vesicles from spruce needle homogenate. We visualized NSHs by light microscopy and cryogenic transmission electron microscopy and assessed them by flow cytometry, dynamic light scattering, ultraviolet–visual spectroscopy, interferometric light microscopy and liquid chromatography–mass spectrometry.Results: We found that the particles consisted of a bilayer membrane and a fluid-like interior. Flow c

Yixue Hu,1 Dongna Wang,2 Tianyu Zhang,2 Meng Lei,3 Yingnan Luo,2 Zhimeng Chen,3 Yuting Li,2 Dandan Duan,2 Liefeng Zhang,1 Yongqiang Zhu1,2 1College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 2School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 3College of Science, Nanjing Forestry University, Nanjing, People’s Republic of ChinaCorrespondence: Liefeng Zhang; Yongqiang Zhu, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.Methods: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.Results: Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration

Chunhong Li,1,&ast; Zhen Wang,1,&ast; Yifeng Zhang,1 Yuqing Zhu,1 Maochang Xu,1 Hui Lei,1 Dan Zhang1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Lei; Dan Zhang, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 17360593759 ; +86 18982700067, Email huilei@swmu.edu.cn; zhangdan@swmu.edu.cnPurpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them.Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model.Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of

Shujie Wang,1,2 Chunyan Shao,2 Xingkai Zhao,1 Yizhe Guo,1 Houhui Song,2 Lida Shen,3 Zhenlei Zhou,1 Zhen Li4,5 1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 2College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3College of Mechanical and Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016, People’s Republic of China; 4College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 5State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, Jiangsu, 210008, People’s Republic of ChinaCorrespondence: Zhenlei Zhou, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel +86 (25) 84395505, Email zhouzl@njau.edu.cn Zhen Li, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel/Fax +86 (25) 84399827, Email lizhen@njau.edu.cnIntroduction: Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo.Methods: In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8

Ana Cepero,1– 3,&ast; Mónica Jiménez-Carretero,4,&ast; Ylenia Jabalera,4 Lidia Gago,1– 3 Cristina Luque,1– 3 Laura Cabeza,1– 3 Consolación Melguizo,1– 3 Concepcion Jimenez-Lopez,4 José Prados1– 3 1Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, 18100, Spain; 2Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, 18071, Spain; 3Biosanitary Research Institute ibs.GRANADA, Granada, 18012, Spain; 4Department of Microbiology, Sciences School, University of Granada, Granada, 18002, Spain&ast;These authors contributed equally to this workCorrespondence: Laura Cabeza; Concepción Jimenez-Lopez, Email lautea@ugr.es; cjl@ugr.esPurpose: The lack of specificity of conventional chemotherapy is one of the main difficulties to be solved in cancer therapy. Biomimetic magnetoliposomes are successful chemotherapy controlled-release systems, hyperthermia, and active targeting agents by functionalization of their surface with monoclonal antibodies. The membrane receptor Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) stands out as colorectal cancer (CRC) biomarker and appears to be related to treatment resistance and the development of metastasis. The aim of this study was to assess the effectiveness and safety of LGR5-targeted biomimetic magnetoliposomes loaded with oxaliplatin (OXA) or 5-fluorouracil (5-FU) in the selective treatment of CRC and their possible application in hyperthermia.Methods: Synthesis, characterization and determination of heating capacity of magnetoliposomes transporting OXA or 5-FU (with and without LGR5 functionalization) were conducted. In vitro antitumoral activity was assayed in multiple colorectal cell lines at different times of exposition. In addition to this, cell internalization was studied by Prussian Blue staining, flow cytometry and fluorescence microscopy. In vivo acute toxicity of m

Jin Tu,1– 3,&ast; Feng Jiang,4,&ast; Jieni Fang,2 Luhua Xu,2 Zhicong Zeng,2 Xuanyue Zhang,1 Li Ba,1 Hanjiao Liu,1,3 Fengxia Lin2 1Department of Nursing, Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 2Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 3Department of Nursing, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 4School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Lin, Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email szlinfx@163.com Hanjiao Liu, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email liuhanjiao000@163.comBackground: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium.Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics.Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analy

Mi Qi, Yajuan Cheng, Ke Liu, Jingxing Cai, Tianyu Liu, Xiaoying Wu, Huili Tang, He Huang, Qinbiao Chen, Xiaoguang Zhou The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Mi Qi; Xiaoguang Zhou, Tel +86-13510794978 ; +86-18818780760, Email qimi@mail.sysu.edu.cn; gzzhouxg@163.comPurpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2−) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct a

Yi Jiang,1,&ast; Xiaoming Liao,1,&ast; Wei Tang,2 Chunyu Huang,3 You Pan,2 Shipeng Ning2 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530000, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, People’s Republic of China; 3Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shipeng Ning, Email nspdoctor@sr.gxmu.edu.cnIntroduction: The presence of cancer stem cells (CSCs) significantly limits the therapeutic efficacy of radiotherapy (RT). Efficient elimination of potential CSCs is crucial for enhancing the effectiveness of RT.Methods: In this study, we developed a biomimetic hybrid nano-system (PMC) composed of MnCO3 as the inner core and platelet membrane (PM) as the outer shell. By exploiting the specific recognition properties of membrane surface proteins, PMC enables precise targeting of CSCs. Sonodynamic therapy (SDT) was employed using manganese carbonate nanoparticles (MnCO3 NPs), which generate abundant reactive oxygen species (ROS) upon ultrasound (US) irradiation, thereby impairing CSC self-renewal capacity and eradicating CSCs. Subsequent RT effectively eliminates common tumor cells.Results: Both in vitro cell experiments and in vivo animal studies demonstrate that SDT mediated by PMC synergistically enhances RT to selectively combat CSCs while inhibiting tumor growth without noticeable side effects.Discussion: Our findings offer novel insights for enhancing the efficacy and safety profiles of RT.Keywords: cancer stem cells clearance, radiosensitization, platelet membrane, sonodynamic therapy, manganese carbonate nanoparticles

Peng Luo,1,&ast; Yi Zhang,2,3,&ast; Maodi Huang,1 Guochen Luo,1 Yaping Ma,1,4 Xin Wang1,4 1Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China; 2Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4Guizhou Provincial Key Laboratory of Medicinal Biotechnology in Colleges and Universities, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Wang, Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China, Tel +86 136 3928 8558, Fax +86-851-2860 8903, Email xin.wang@zmu.edu.cnIntroduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo).Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron mic

Kaming Xue,1 Bobin Mi2 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Bobin Mi, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email mibobin@hust.edu.cnAbstract: Chronic kidney diseases (CKD) present a formidable global health challenge, characterized by a deficiency of effective treatment options. Extracellular vesicles (EVs), recognized as multifunctional drug delivery systems in biomedicine, have gained accumulative interest. Specifically, engineered EVs have emerged as a promising therapeutic approach for targeted drug delivery, potentially addressing the complexities of CKD management. In this review, we systematically dissect EVs, elucidating their classification, biogenesis, composition, and cargo molecules. Furthermore, we explore techniques for EV engineering and strategies for their precise renal delivery, focusing on cargo loading and transportation, providing a comprehensive perspective. Moreover, this review also discusses and summarizes the diverse therapeutic applications of engineered EVs in CKD, emphasizing their anti-inflammatory, immunomodulatory, renoprotective, and tissue-regenerating effects. It critically evaluates the challenges and limitations in translating EV therapies from laboratory settings to clinical applications, while outlining future prospects and emerging trends.Keywords: extracellular vesicles, nanomaterials, chronic kidney diseases, drug delivery systems, application

Man Sun,1 Huan Zhang,1 Jiayi Liu,1 Jiayi Chen,1 Yaxin Cui,1 Simiao Wang,1 Xiangyu Zhang,2 Zhaogang Yang1 1School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310020, People’s Republic of ChinaCorrespondence: Xiangyu Zhang; Zhaogang Yang, Tel/Fax +86-431-85155320, Email 3314023@zju.edu.cn; zhaogangyang@jlu.edu.cnAbstract: Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.Keywords: extracellular vesicles, gene therapy, drug delivery s

Milena Fronza Broering,1,2 Pedro Leonidas Oseliero Filho,3,4 Pâmela Pacassa Borges,1 Luis Carlos Cides da Silva,3 Marcos Camargo Knirsch,5 Luana Filippi Xavier,1 Pablo Scharf,1 Silvana Sandri,1 Marco Antonio Stephano,5 Fernando Anselmo de Oliveira,6 Ibrahim M Sayed,2 Lionel Fernel Gamarra,6 Soumita Das,2 Márcia CA Fantini,3 Sandra HP Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; 2Department of Biomedical and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA; 3Department of Applied Physics, Physics Institute, University of Sao Paulo, São Paulo, Brazil; 4Materials Innovation Factory, University of Liverpool, Liverpool, MSY, UK; 5Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; 6Instituto do Cérebro, Instituto Israelita de Ensino e Pesquisa, Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein, São Paulo, SP, BrazilCorrespondence: Sandra HP Farsky, Email sfarsky@usp.brIntroduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology.Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut.Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26

Yuanyuan Zhao,1 Yang Liu,1 Cheng Lu,1 Daokuan Sun,2 Shiqi Kang,1 Xin Wang,2,&ast; Laijin Lu1,&ast; 1Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Laijin Lu, Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Tel +86-13756661203, Fax +86 431 84808391, Email ljlu@jlu.edu.cn Xin Wang, School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China, Tel +86-18 626 655 395, Fax +86 431 84 808 391, Email wang_xin@jlu.edu.cnBackground: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo.Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated.Results: rGOFs exhibited

Meng-Ru Zhang,1,2,&ast; Lin-Lin Fang,3,&ast; Yang Guo,1 Qin Wang,1 You-Jie Li,1 Hong-Fang Sun,1 Shu-Yang Xie,1 Yan Liang1 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 2Department of Clinical Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 3RemeGen Co., Ltd, YanTai, ShanDong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shu-Yang Xie, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China, Tel/Fax +86 535 6913335 ; +86 535 6913166, Email 18766567201@163.com; xieshuyang@bzmc.edu.cnAbstract: Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming “cold” tumors into “hot” tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-re

Hyun Ho Shin,1,&ast; Junyoung Park,2,&ast; Yeo-Jin Kim,3 Donghyeon Kim,2 Eun-Jung Jin,2,4 Ji Hyun Ryu1,3,4 1Department of Chemical Engineering, Wonkwang, University, Iksan, Jeonbuk, 54538, Republic of Korea; 2Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 3Department of Carbon Convergence Engineering, Smart Convergence Materials Analysis Center, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 4Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Ji Hyun Ryu, Department of Carbon Convergence Engineering, Iksan, Jeonbuk, 54538, Republic of Korea, Email jhryu4816@wku.ac.kr Eun-Jung Jin, Department of Biological Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea, Email jineunjung@wku.ac.krIntroduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects.Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1β (IL-1β)

Sushmita Negi,1,2,&ast; Nikunj Tandel,3,&ast; Neeraj K Garg,4 Prakriti Sharma,1 Rajinder Kumar,1 Praveen Sharma,1 Reetesh Kumar,5 Sheetal Saini,1 Aman Sharma,6 Rajeev K Tyagi1,2 1Biomedical Parasitology and Translational-Immunology Lab, Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, 160036, India; 2Academy of Scientific and Innovation Research (Acsir), Ghaziabad, 201002, India; 3Institute of Science, Nirma University, Ahmedabad, Gujarat, India; 4University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India; 5Faculty of Agricultural Sciences, Institute of Applied Sciences and Humanities, GLA University, Mathura, Uttar Pradesh, India; 6Clinical Immunology and Rheumatology Wing, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India&ast;These authors contributed equally to this workCorrespondence: Rajeev K Tyagi, Biomedical Parasitology and Translational-immunology Lab, Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Sec-39a, Chandigarh, 160036, India, Tel +91-172-6665278; +91-172-6665279, Email rajeevtyagi@imtech.res.in; rajeev.gru@gmail.comBackground: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events.Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macropha

Fei Shu,&ast; Hong Chen,&ast; Zhihao Zhang, Zhiyue Dun, Weijin Lv, Wangxinyue Sun, Mei Liu Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Liu, Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China, Tel +86-25-69593081, Fax +86-25-69593186, Email liumei2017@njmu.edu.cnIntroduction: Poor interfacial bonding between the fibers and resin matrix in fiber-reinforced composites (FRCs) is a significant drawback of the composites. To enhance the mechanical properties of FRC, fibers were modified by depositing SiO2 nanofilms via the atomic layer deposition (ALD) technique. This study aims to evaluate the effect of ALD treatment of the fibers on the mechanical properties of the FRCs.Methods: The quartz fibers were modified by depositing different cycles (50, 100, 200, and 400) of SiO2 nanofilms via the ALD technique and FRCs were proposed from the modified fibers. The morphologies, surface characterizations of nanofilms, mechanical properties, and cytocompatibility of FRCs were systematically investigated. Moreover, the shear bond strength (SBS) of FRCs to human enamel was also evaluated.Results: The SEM and SE results showed that the ALD-deposited SiO2 nanofilms have good conformality and homogeneity. According to the results of FTIR and TGA, SiO2 nanofilms and quartz fiber surfaces had good chemical combinations. Three-point bending tests with FRCs showed that the deposited SiO2 nanofilms effectively improved FRCs’ strength and Group D underwent 100 de

Debiao Xiang,1– 3 Lili Zhou,4 Rui Yang,1,4 Fang Yuan,1– 3 Yilin Xu,4 Yuan Yang,1,4 Yong Qiao,1– 3 Xin Li1– 3 1Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan Province, People’s Republic of China; 2Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Changsha, Hunan Province, People’s Republic of China; 3The Clinical Application Research Institute of Antibiotics in Changsha, Changsha, Hunan Province, People’s Republic of China; 4College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Xin Li, 176 Laodong West Road, Tianxin District, Changsha, Hunan Province, People’s Republic of China, Tel +86 0731-85171320, Email xin-li@cssdsyy.comAbstract: Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting syst

Dunling Xia,1 Zongqing Lu,1 Shuai Li,1 Pu Fang,1 Chun Yang,2 Xiaoyan He,3 Qinghai You,1 Gengyun Sun1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Emergency Intensive Care Unit, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3School of Life Sciences, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qinghai You; Gengyun Sun, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Sanli’an Street, Shushan District, Hefei, Anhui Province, 230032, People’s Republic of China, Tel +86 551 6292 2913, Fax +86 551 6292 2752, Email amormor@126.com; sungengy@126.comIntroduction: Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are commonly occurring devastating conditions that seriously threaten the respiratory system in critically ill patients. The current treatments improve oxygenation in patients with ALI/ARDS in the short term, but do not relieve the clinical mortality of patients with ARDS.Purpose: To develop the novel drug delivery systems that can enhance the therapeutic efficacy of ALI/ARDS and impede adverse effects of drugs.Methods: Based on the key pathophysiological process of ARDS that is the disruption of the pulmonary endothelial barrier, bilirubin (Br) and atorvastatin (As) were encapsulated into an intelligent reactive oxygen species (ROS)-responsive nanocarrier DSPE-TK-PEG (DPTP) to form nanoparticles (BA@DPTP) in which the thioketal bonds could be triggered by high ROS levels in the ALI tissues.Results: BA@DPTP could accumulate in inflammatory pulmonary sites through passive targeting strategy and intelligently release Br and As only in the inflammatory tissue via ROS-responsive bond, thereby enhancing the drugs effectiveness and markedly reducing

Yuting Feng, Xue Bao, Jinxuan Zhao, Lina Kang, Xuan Sun, Biao Xu Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Xuan Sun; Biao Xu, Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email sunxuan891119@163.com; xubiao62@nju.edu.cnIntroduction: Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury.Methods: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro.Results: MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also coul

Arif Budiman,1 Gracia Anastasya,1 Annisa Luthfiyah Handini,1 Ira Novianty Lestari,2 Laila Subra,3 Diah Lia Aulifa2 1Department of Pharmaceutics and Pharmaceutical Technology, Universitas Padjadjaran, Bandung, Indonesia; 2Department of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Bandung, Indonesia; 3Department of Pharmacy, Universiti Geomatika Malaysia, Kuala Lumpur, MalaysiaCorrespondence: Diah Lia Aulifa, Department of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Jl, Raya Bandung-Sumedang Km. 21, Bandung, 45363, Indonesia, Email diah.lia@unpad.ac.idAbstract: Solid oral dosage forms are mostly preferred in pharmaceutical formulation development due to patient convenience, ease of product handling, high throughput, low manufacturing costs, with good physical and chemical stability. However, 70% of drug candidates have poor water solubility leading to compromised bioavailability. This phenomenon occurs because drug molecules are often absorbed after dissolving in gastrointestinal fluid. To address this limitation, delivery systems designed to improve the pharmacokinetics of drug molecules are needed to allow controlled release and target-specific delivery. Among various strategies, amorphous formulations show significantly high potential, particularly for molecules with solubility-limited dissolution rates. The ease of drug molecules to amorphized is known as their glass-forming ability (GFA). Specifically, drug molecules categorized into class III based on the Taylor classification have a low recrystallization tendency and high GFA after cooling, with substantial “glass stability” when heated. In the last decades, the application of mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS) has gained significant attention in various investigations and the pharmaceutical industry. This is attributed to the unique physicochemical properties of MSNs, including high loading capacity, recrystalliza

Adi Yugatama,1,2,&ast; Ya-Lin Huang,1,&ast; Ming-Jen Hsu,3 Jia-Pei Lin,1 Fang-Ching Chao,4 Jenny KW Lam,5 Chien-Ming Hsieh1,5,6 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan; 2Department of Pharmacy, Sebelas Maret University, Surakarta, 57126, Indonesia; 3Department of Pharmacology, Taipei Medical University, Taipei, 11031, Taiwan; 4CNRS UMR 8612, Institut Galien Paris-Saclay, Université Paris-Saclay, Orsay, 91400, France; 5Department of Pharmaceutics, School of Pharmacy, University College, London, WC1N 1AX, UK; 6Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan&ast;These authors contributed equally to this workCorrespondence: Jenny KW Lam, Department of Pharmaceutics, School of Pharmacy, University College London, 29– 39 Brunswick Square, London, WC1N 1AX, UK, Email jenny.lam@ucl.ac.uk Chien-Ming Hsieh, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan, Email cmhsieh@tmu.edu.twBackground: Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC). Nanogels (NGs) offer a novel oral drug delivery system, ideal for hydrophilic compounds like GEM. This study aims to develop NGs tailored for GEM delivery, with the goal of enhancing cellular uptake and gastrointestinal permeability for improved administration in PDAC patients.Methods: We developed cross-linked NGs via photopolymerization of methacryloyl for drug delivery of GEM. We reveal characterization, cytotoxicity, and cellular uptake studies in Caco-2 and MIA PaCa-2 cells. In addition, studies of in vitro permeability and pharmac