Search

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino) ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor. [ABSTRACT FROM AUTHOR]

Currently three major problems seriously limit the practical application of cancer photodynamic therapy (PDT): (i) the hypoxic tumor microenvironment (TME); (ii) low generation efficiency of toxic reactive oxygen species (ROS) in aggregates and (iii) shallow tissue penetration depth of excitation light. Very limited approaches are available for addressing all the above three problems with a single design. Herein, a rational "three birds with one stone" molecular and nanoengineering strategy is demonstrated: a photodynamic nanoplatform U‐Ir@PAA‐ABS based on the covalent combination of lanthanide‐doped upconversion nanoparticles (UCNPs) and an AIE‐active dinuclear Ir(III) complex provides a low oxygen concentration‐dependent type‐I photochemical process upon 980 nm irradiation by Föster resonance energy transfer (FRET). U‐Ir@PAA‐ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation, inducing a dual‐mode cell death mechanism by apoptosis and ferroptosis. Taken together, the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors. [ABSTRACT FROM AUTHOR]

The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events. Thus, timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis. In this work, a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities. The iodinated contrast agents (ICA), phenylboronic acid modified astaxanthin and oxidized-dextran (oxDEX) jointly construct the nanoparticles loaded with the lipid-specific probe LFP. LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis. The X-CT signals of ICA execute the location of early-stage plaques, while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques. Meanwhile, the treatment based on astaxanthin is performed for restraining the progression of plaques. Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway, which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing. The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques, which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.

BACKGROUND: The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment. On the other hand, although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization, the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE: To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS: SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions (Fe2+) and divalent cobalt ions (Co2+) (Fe-Co/ZIF-8@SLC-0111) was synthesized by ion-exchange reaction and self-assembly, and loaded with hyaluronic acid (HA) by electrostatic adsorption, followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA (abbreviated as FC-S). Meanwhile, nanoparticles Fe-Co/ZIF-8-HA (abbreviated as FC) without SLC-0111 were synthesized by the same method. The nanocomposite platform was tested for particle size, zeta potential, surface morphology, in vitro reactive oxygen species generation, and ability to consume glutathione. Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects. The cytotoxicity of FC-S was detected by CCK-8 assay. Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S. In addition to H2O2, the effects of FC-S and FC on intracellular pH, carbonic anhydrase 9 protein expression, cell viability and apoptosis, intracellular reactive oxygen species and glutathione content, and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION: (1) The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure, uniform size and good dispersion. Its particle size was about 323 nm; zeta potential was about -11.1 mV, and the nanoplatform had a certain reactive oxygen species generation capacity in vitro. (2) FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes. When the mass concentration of FC-S was ≤ 20 µg/mL, there was no obvious cytotoxicity to MG-63 cells and L929 cells, and 20 µg/mL FC-S was selected to act on MG-63 cells in subsequent experiments. (3) Compared with FC group, the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased (P < 0.01); the intracellular acidic environment was enhanced; the content of reactive oxygen species was increased (P < 0.001); the mitochondrial damage was aggravated; the number of dead cells was increased, and the apoptosis rate was increased (P < 0.001). (4) The results indicate that FC-S, as a novel composite nanoplatform, can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production, thus enhancing the efficacy of chemodynamic therapy. [ABSTRACT FROM AUTHOR]

Real‐time monitoring the therapeutic process of sonodynamic therapy (SDT) is essential to optimize the treatment course in time and eventually improve the efficacy. The generation of singlet oxygen (1O2) is a quintessential characteristic of SDT, which permits non‐invasive monitoring of SDT by real‐time imaging of 1O2 inside the tumor. Nonetheless, the majority of probes are unable to measure 1O2 in real time because of its short half‐life and strong oxidative capacity. Here, the study constructs a ratiometric nanoplatform (DTPI) utilizing two fluorescent probes and the sonosensitizer TiO2. The poisonous 1O2 generated by DTPI following ultrasonic (US) radiation efficiently destroys tumor cells. The structural disruption of fluorescent dye IR‐1061 by 1O2 leads to a reduction in the DTPI fluorescence signal at 1100 nm, while US radiation has no impact on the fluorescence signal at 1550 nm. Thus, DTPI provides a precise and consistent reflection of the treatment efficacy at the tumor site, leveraging the ratiometric fluorescence signal and variations in oxygen content throughout the treatment process. This ratiometric‐fluorescence‐based reflection strategy establishes an effective and dependable platform for the real‐time monitoring and assessment of the cancer therapeutic effect through ratiometric probes. [ABSTRACT FROM AUTHOR]

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. Treating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo , making it a promising treatment for severely infected skin injuries. [Display omitted] [ABSTRACT FROM AUTHOR]

Oligodeoxynucleotides (ODNs) containing unmethylated cytosine–phosphate–guanosine (CpG) motifs are readily recognized by Toll-like receptor 9 on immune cells, trigger an immunomodulatory cascade, induce a Th1 -biased immune milieu, and have great potential as an adjuvant in cancer vaccines. In this study, a green one-step synthesis process was adopted to prepare an amino-rich metal–organic nanoplatform (FN). The synthesized FN nanoplatform can simultaneously and effectively load model tumor antigens (OVA)/autologous tumor antigens (dLLC) and immunostimulatory CpG ODNs with an unmodified PD backbone and a guanine quadruplex structure to obtain various cancer vaccines. The FN nanoplatform and immunostimulatory CpG ODNs generate synergistic effects to enhance the immunogenicity of different antigens and inhibit the growth of established and distant tumors in both the murine E.G7-OVA lymphoma model and the murine Lewis lung carcinoma model. In the E.G7-OVA lymphoma model, vaccination efficiently increases the CD4+, CD8+, and tetramer+CD8+ T cell populations in the spleens. In the Lewis lung carcinoma model, vaccination efficiently increases the CD3+CD4+ and CD3+CD8+ T cell populations in the spleens and CD3+CD8+, CD3−CD8+, and CD11b+CD80+ cell populations in the tumors, suggesting the alteration of tumor microenvironments from cold to hot tumors. [ABSTRACT FROM AUTHOR]

Abstract Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines. Graphical Abstract

Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines. [ABSTRACT FROM AUTHOR]

Atherosclerosis can cause severe cardiovascular disease, which is usually diagnosed in late stages with life‐threatening complications. The lack of obvious symptoms limits its early diagnosis and timely treatment. In this work, a theranostic nanoplatform PGA@PMP is constructed for targeting photoacoustic diagnosis and a "hand‐in‐hand" immunoregulation of early‐stage atherosclerosis. Coated with biomimetic platelet membrane, PGA@PMP can actively target to the pathological endothelium and respond to the reactive oxygen species (ROS) in lesions for further disassembly and releasing photoacoustic probe along with immune‐regulate complex GWAS. The photoacoustic probe performs a noninvasive imaging with distinct recognition of plaques. In company, triggered by local cathepsin B, GWAS can be degraded for respective regulation on inducing M2 macrophages and stimulating regulatory T (Treg) cells. The transforming growth factor beta (TGF‐β) expressed by up‐regulated M2 macrophages also intensifies the Treg cell differentiation, which synergistically inhibits the foam cell formation and rebuilds a well‐balanced immune microenvironment. The in vivo evaluations suggest that the "hand‐in‐hand" strategy on regulating macrophages polarization and T cell differentiation indicates the restraint on atherosclerotic progression and the reversal of formed lesions even under high‐fat diet. Together, PGA@PMP provides an integrated solution for targeting theranostics of early‐stage atherosclerosis and delivers an exciting outcome of reversing the formed lesions. [ABSTRACT FROM AUTHOR]

As an efficient, non-invasive, low-side-effect, and highly selective cancer therapy, photodynamic therapy (PDT) is used to treat various malignant tumors. However, the inefficiency of dealing with deep tumors and metastatic lesions highly limits the use of PDT. Immunogenic cell death (ICD) is a particular form of tumor cell death that could elicit a tumor-special immune response, leading to a systemic anti-tumor effect and providing therapeutic benefits for metastatic lesions. In this regard, it is crucial to enhance the ability of PDT to induce ICD. Luckily, advanced nanotechnology created many promising ways to improve the immunogenicity of PDT and achieve photoimmunotherapy. This review summarizes the emerging strategies for triggering immunogenic cell death via nanoplatform-enhanced PDT, with particular emphasis on their advantages in photoimmunotherapy. We highlight the nanoplatforms classified according to the basic principles of photodynamic therapy and immunogenic cell death, which provides a valuable reference for the design of nanoplatform for photoimmunotherapy. In addition, we also discuss the current situation and prospect of nano-based photoimmunotherapy in clinical studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Monoclonal antibodies targeting CTLA-4, PD-1/PD-L1 axis, and LAG-3, have shown unprecedented clinical success in melanoma. However, such immune checkpoint blockade (ICB) therapies failed to initiate primary immune responses or with limited durability. Here, we reviewed the mechanisms eliciting intrinsic resistance and adaptive resistance in melanoma patients. Furthermore, we introduced emerging nano-strategies to overcome the ICB by either enhancing tumour cell phagocytosis through checkpoint-mediated internalization or devising nano-immunomodulators for ICB combination therapy. These strategies may lead to clinical translations in the future.

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules. Using a squamous cell carcinoma model, we demonstrated that a pH-sensitive fusogenic peptide -modification of BMSC-EVs achieved targetability in the microenvironment of a hypoxic tumor to deliver anti-tumor drugs. Using EGFR+HER2- and EGFR-HER2+ breast cancer models, we demonstrated that anti-EGFR and anti-HER2 modifications of BMSC-EVs were able to specifically deliver drugs to EGFR+ and HER2+ tumors, respectively. Using a collagen-induced arthritis model, we confirmed that anti-IL12/IL23-modified BMSC-EVs specifically accumulated in the arthritic joint and alleviated inflammation. Administration of SA-overexpressing BMSC-EVs has limited immunogenicity and high safety in vivo , suggesting that BMSC-derived EVs are ideal drug delivery vehicle. These representative scenarios of targeting modification suggest that, using different biotinylated molecules, the SA-overexpressing BMSC-EVs could be endowed with different targetabilities, which allows BMSC-EVs to serve as a versatile platform for targeted drug delivery under various situations. [Display omitted] • SAV engineered BMSCs yield EVs with outside of membrane expression of SAV(SAV-EVs). • SAV-EVs are highly affinity with biotinylated monoclonal antibodies. • Replacing different biotinylated monoclonal antibodies can endow SAV-EVs with diverse targeting properties. • Loading with different drugs to SA-EVs can achieve the purpose of targeting therapy. [ABSTRACT FROM AUTHOR]

Epitaxy is the process of crystallization of monocrystalline layers and nanostructures on a crystalline substrate. It allows for the crystallization of various semiconductor layers on a finite quantity of semiconductor substrates, like GaAs, InP, GaP, InGaP, GaP, and many others. The growth of epitaxial heterostructures is very complicated and requires special conditions and the precise control of the growth temperature, the pressure in the reactor, and the flow of the precursors. It is used to grow epitaxial structures in lasers, diodes, detectors, photovoltaic structures, and so on. Semiconductors themselves are not suitable materials for application in surface-enhanced Raman spectroscopy (SERS) due to poor plasmonic properties in the UV/VIS range caused by missing free electrons in the conduction band due to the existing band gap. A plasmonic material is added on top of the nanostructured pattern, allowing for the formation of mixed photon–plasmon modes called localized surface plasmon-polaritons which stand behind the SERS effect. Typically, gold and silver are used as functional plasmonic layers. Such materials could be deposited via chemical or physical process. Attention has also been devoted to other plasmonic materials, like ones based on the nitrides of metals. The SERS performance of a functional surface depends both on the response of the plasmonic material and the morphology of the underlying semiconductor epitaxial layer. In the context of SERS, epitaxial growth allows for the fabrication of substrates with well-defined 3D nanostructures and enhanced electromagnetic properties. In this work, we described the possible potential plasmonic modification, composed of various coatings such as noble metals, TiN, and others, of well-developed epitaxial nanostructures for the construction of a new type of highly active SERS platforms. This abstract also highlights the role of epitaxial growth in advancing SERS, focusing on its principles, methods, and impact. Furthermore, this work outlines the potential of epitaxial growth to push the boundaries of SERS. The ability to design substrates with tailored plasmonic properties opens avenues for ultralow concentration detection. [ABSTRACT FROM AUTHOR]

There is a serious threat to public health posed by the rapid spread of methicillin-resistant Staphylococcus aureus (MRSA). Photodynamic sterilization is the most effective method of combating bacterial infection, especially multidrug-resistant bacterial infection. In this study, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal–organic framework material, were used to encapsulate the indocyanine green (ICG, a potent PS); after that, hyaluronic acid (HA) coating was applied to the nanoparticle to create a host cell-tracking nanoplatform (ICG@ZIF-8/HA). Upon near-infrared light irradiation, ICG@ZIF-8/HA exhibit excellent efficacy in producing reactive oxygen species (ROS) and killing multidrug-resistant bacteria in vitro. After the tail vein injection, ICG@ZIF-8/HA can precisely deliver to lung infection sites, and display an effective PDT-based elimination of multidrug-resistant bacteria in mouse lung infection models. These results suggest that the ICG@ZIF-8/HA nanoplatform may exhibit potent curative effects on infectious diseases.

Oligodeoxynucleotides (ODNs) containing unmethylated cytosine–phosphate–guanosine (CpG) motifs are readily recognized by Toll-like receptor 9 on immune cells, trigger an immunomodulatory cascade, induce a Th1 -biased immune milieu, and have great potential as an adjuvant in cancer vaccines. In this study, a green one-step synthesis process was adopted to prepare an amino-rich metal–organic nanoplatform (FN). The synthesized FN nanoplatform can simultaneously and effectively load model tumor antigens (OVA)/autologous tumor antigens (dLLC) and immunostimulatory CpG ODNs with an unmodified PD backbone and a guanine quadruplex structure to obtain various cancer vaccines. The FN nanoplatform and immunostimulatory CpG ODNs generate synergistic effects to enhance the immunogenicity of different antigens and inhibit the growth of established and distant tumors in both the murine E.G7-OVA lymphoma model and the murine Lewis lung carcinoma model. In the E.G7-OVA lymphoma model, vaccination efficiently increases the CD4+, CD8+, and tetramer+CD8+ T cell populations in the spleens. In the Lewis lung carcinoma model, vaccination efficiently increases the CD3+CD4+ and CD3+CD8+ T cell populations in the spleens and CD3+CD8+, CD3−CD8+, and CD11b+CD80+ cell populations in the tumors, suggesting the alteration of tumor microenvironments from cold to hot tumors.

The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy (SDT), a noninvasive and effective therapeutic strategy, has broadened the way toward dealing with antibiotic-resistant bacteria and biofilms, which base on ultrasound (US) with sonosensitizer. Sonosensitizer, based on small organic molecules or inorganic nanoparticles, is essential to the SDT process. Thus, it is meaningful to design a sonosensitizer-loaded nanoplatform and synthesize the nanoplatform with an efficient SDT effect. In this review, we initially summarize the probable SDT-based antibacterial mechanisms and systematically discuss the current advancement in different SDT-based nanoplatform (including nanoplatform for organic small-molecule sonosensitizer delivery and nanoplatform as sonosensitizer) for bacterial infection therapy. In addition, the biomedical applications of SDT-involved multifunctional nanoplatforms are also discussed. We believe the innovative SDT-based nanoplatforms would become a highly efficient next-generation noninvasive therapeutic tool for combating bacterial infection.

Background and Aims: Cytotoxicity is a key disadvantage of using chemotherapeutic drugs to treat cancer. This can be overcome by encapsulating chemotherapeutic drugs in suitable carriers for targeted delivery, allowing them to be released only at the cancerous sites. Herein, we aim to review the recent scientific developments in the utilization of nanotechnology‐based drug delivery systems for treating oral malignancies that can lead to further improvements in clinical practice. Methods: A comprehensive literature search was conducted on PubMed, Google Scholar, ScienceDirect, and other notable databases to identify recent peer‐reviewed clinical trials, reviews, and research articles related to nanoplatforms and their applications in oral cancer treatment. Results: Nanoplatforms offer a revolutionary strategy to overcome the challenges associated with conventional oral cancer treatments, such as poor drug solubility, non‐specific targeting, and systemic toxicity. These nanoscale drug delivery systems encompass various formulations, including liposomes, polymeric nanoparticles, dendrimers, and hydrogels, which facilitate controlled release and targeted delivery of therapeutic agents to oral cancer sites. By exploiting the enhanced permeability and retention effect, Nanoplatforms accumulate preferentially in the tumor microenvironment, increasing drug concentration and minimizing damage to healthy tissues. Additionally, nanoplatforms can be engineered to carry multiple drugs or a combination of drugs and diagnostic agents, enabling personalized and precise treatment approaches. Conclusion: The utilization of nanoplatforms in oral cancer treatment holds significant promise in revolutionizing therapeutic strategies. Despite the promising results in preclinical studies, further research is required to evaluate the safety, efficacy, and long‐term effects of nanoformulations in clinical settings. If successfully translated into clinical practice, nanoplatform‐based therapies have the potential to improve patient outcomes, reduce side effects, and pave the way for more personalized and effective oral cancer treatments. Highlights: Surgery, radiation, and chemotherapy are the solely available treatments for cancer.Oral cancer includes cancers of the mouth and the back of the throat.With selective targeting and distribution of these anticancer medications to tumor tissues, nanotechnology has traditionally been used in cancer therapy to enhance pharmacokinetics and lower the systemic toxicity of chemotherapy.Nanotechnology has the potential to overcome many shortcomings of chemotherapy, enable drugs to precisely target tumor cells, reduce unfavorable side effects on nearby healthy tissues, and thus pave the way to create cutting‐edge treatments for oral cancer. [ABSTRACT FROM AUTHOR]

Despite its introduction more than three decades ago, gene therapy has fallen short of its expected potential for the treatment of a broad spectrum of diseases and continues to lack widespread clinical use. The fundamental limitation in clinical translatability of this therapeutic modality has always been an effective delivery system that circumvents degradation of the therapeutic nucleic acids, ensuring they reach the intended disease target. Plasmid DNA (pDNA) for the purpose of introducing exogenous genes presents an additional challenge due to its size and potential immunogenicity. Current pDNA methods include naked pDNA accompanied by electroporation or ultrasound, liposomes, other nanoparticles, and cell-penetrating peptides, to name a few. While the topic of numerous reviews, each of these methods has its own unique set of limitations, side effects, and efficacy concerns. In this review, we highlight emerging uses of exosomes for the delivery of pDNA for gene therapy. We specifically focus on bovine milk and colostrum-derived exosomes as a nano-delivery "platform". Milk/colostrum represents an abundant, scalable, and cost-effective natural source of exosomes that can be loaded with nucleic acids for targeted delivery to a variety of tissue types in the body. These nanoparticles can be functionalized and loaded with pDNA for the exogenous expression of genes to target a wide variety of disease phenotypes, overcoming many of the limitations of current gene therapy delivery techniques. [ABSTRACT FROM AUTHOR]

Abstract Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed.

Thermal ablation (TA) as an effective method treating hepatocellular carcinoma (HCC) in clinics is facing great challenges of high recurrence and metastasis. Although immune-checkpoint blockade (ICB)-based immunotherapy has shown potential to inhibit recurrence and metastasis, the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments. The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells (TIDCs) which leads to an inferior immune response to distant tumor growth and metastasis. Herein, an antigen-capturing nanoplatform, whose surface was modified with mannose as a targeting ligand, was constructed for co-delivering tumor-associated antigens (TAAs) and m6A demethylases inhibitor (i.e., fat mass and obesity associated gene (FTO) inhibitor) into TIDCs. In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells (DCs) maturation, improves tumor infiltration of effector T cells and generates immune memory, which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis. Therefore, the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.

Abstract Background Nanomedicine offers great potentials for theranostic studies via providing higher efficacy and safety levels. This work aimed to develop and evaluate a new nanoplatform as a tumor theranostic probe. Results Carboxyl-functionalized graphene oxide nanosheets (FGO) was well synthesized from graphite powder and then conjugated with folic acid to act as a targeted nano-probe. Full characterization and in vitro cytotoxicity evaluation were conducted; besides, in vivo bio-evaluation was attained via intrinsic radioiodination approach in both normal and tumor-bearing Albino mice. The results indicated that FGO as well as conjugated graphene oxide nanosheets (CGO) are comparatively non-toxic to normal cells even at higher concentrations. Pharmacokinetics of FGO and CGO showed intensive and selective uptake in the tumor sites where CGO showed high T/NT of 7.27 that was 4 folds of FGO at 1 h post injection. Additionally, radioiodinated-CGO (ICGO) had declared a superior prominence over the previously published tumor targeted GO radiotracers regarding the physicochemical properties pertaining ability and tumor accumulation behavior. Conclusions In conclusion, ICGO can be used as a selective tumor targeting agent for cancer theranosis with aid of I-131 that has a maximum beta and gamma energies of 606.3 and 364.5 keV, respectively.

Abstract Background and Aims Cytotoxicity is a key disadvantage of using chemotherapeutic drugs to treat cancer. This can be overcome by encapsulating chemotherapeutic drugs in suitable carriers for targeted delivery, allowing them to be released only at the cancerous sites. Herein, we aim to review the recent scientific developments in the utilization of nanotechnology‐based drug delivery systems for treating oral malignancies that can lead to further improvements in clinical practice. Methods A comprehensive literature search was conducted on PubMed, Google Scholar, ScienceDirect, and other notable databases to identify recent peer‐reviewed clinical trials, reviews, and research articles related to nanoplatforms and their applications in oral cancer treatment. Results Nanoplatforms offer a revolutionary strategy to overcome the challenges associated with conventional oral cancer treatments, such as poor drug solubility, non‐specific targeting, and systemic toxicity. These nanoscale drug delivery systems encompass various formulations, including liposomes, polymeric nanoparticles, dendrimers, and hydrogels, which facilitate controlled release and targeted delivery of therapeutic agents to oral cancer sites. By exploiting the enhanced permeability and retention effect, Nanoplatforms accumulate preferentially in the tumor microenvironment, increasing drug concentration and minimizing damage to healthy tissues. Additionally, nanoplatforms can be engineered to carry multiple drugs or a combination of drugs and diagnostic agents, enabling personalized and precise treatment approaches. Conclusion The utilization of nanoplatforms in oral cancer treatment holds significant promise in revolutionizing therapeutic strategies. Despite the promising results in preclinical studies, further research is required to evaluate the safety, efficacy, and long‐term effects of nanoformulations in clinical settings. If successfully translated into clinical practice, nanoplatform‐based therapies have the potential to improve patient outcomes, reduce side effects, and pave the way for more personalized and effective oral cancer treatments.

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields. [ABSTRACT FROM AUTHOR]

Pharmaceutical pollutants such as tetracycline (TC) pose a growing global threat to aquatic and terrestrial biodiversity. Developing new methods for the degradation of these pollutants would be a significant advancement in their management. The progress in the development of synthetic enzymes based on nanomaterials has resulted in their replacement for natural enzymes with higher performance quality. In this work, a magnetite/Gd3+/β-cyclodextrin nanoplatform was prepared and used for TC degradation for the first time. The characterization studies were carried out using various methods, including SEM, XRD, and FTIR. The peroxidase-mimic activity of the synthesized nanoplatform was evaluated using a colorimetric assay. Kinetic parameters, including Km and Vmax, were obtained using TMB (3,3′,5,5′-tetramethylbenzidine) and H2O2. The results indicated that prepared particles had a lower Km value than horseradish peroxidase (HRP), which confirmed the higher affinity of the prepared nanoplatform toward its substrates. We also demonstrated that our recyclable nanoplatform (3 mg/mL) was able to degrade 82% of TC (4.5 mM) in 85 min without any initiator such as light or ultrasonic waves. Collectively, these results confirmed the high affinity of the synthesized nanoplatform toward desired substrates, including TC. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Abstract Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.

Chunkang Liu,1,&ast; Kunzhe Wu,2,&ast; Huan Gao,3 Jianyang Li,3 Xiaohua Xu3 1Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Xu, Email xu_xh@jlu.edu.cnAbstract: Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), is the most common form of chronic kidney disease (CKD) and a leading cause of renal failure in end-stage renal disease. No currently available treatment can achieve complete cure. Traditional treatments have many limitations, such as painful subcutaneous insulin injections, nephrotoxicity and hepatotoxicity with oral medication, and poor patient compliance with continual medication intake. Given the known drawbacks, recent research has suggested that nanoparticle-based drug delivery platforms as therapeutics may provide a promising strategy for treating debilitating diseases such as DN in the future. This administration method provides multiple advantages, such as delivering the loaded drug to the precise target of action and enabling early prevention of CKD progression. This article discusses the development of the main currently used nanoplatforms, such as liposomes, polymeric NPs, and inorganic NPs, as well as the prospects and drawbacks of nanoplatform application in the treatment of CKD.Keywords: diabetic nephropathy, DN, nanoplatform, route of administration

Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed. [ABSTRACT FROM AUTHOR]

Gas therapy (GT) exhibits great potential for clinical application due to its high therapeutic efficiency, low systemic side effects, and biosafety, thereinto, a multifunctional nanoplatform is generally needed for controllable gas release and precise delivery to tumor tissue. In this review, the recent development of multifunctional nanoplatforms for efficient tumor delivery of stimuli-responsive gas-releasing molecules (GRMs), which could be triggered by either exogenous physical or endogenous tumor microenvironment (TME) is summarized. The reported therapeutic gas molecules, including oxygen (O2), hydrogen sulfide (H2S), nitric oxide (NO), hydrogen (H2), and carbon monoxide (CO), etc., could directly influence or change the pathological status. Additionally, abundant nanocarriers have been employed for gas delivery into cancer region, such as mesoporous silica nanoparticles (MSNs), metal-organic frameworks (MOFs), two-dimensional (2D) nanomaterials, and liposomes, as well as non-nanocarriers including inorganic and organic nanoparticles. In the end, the outlooks of current challenges of GT and GRMs delivery nanoplatforms as well as the prospects of future clinical applications are proposed. [ABSTRACT FROM AUTHOR]

Herein, we report, for the first time, a unique stiffness‐transformable manganese oxide hybridized mesoporous organosilica nanoplatform (MMON) for enhancing tumor therapeutic efficacy. The prepared MMONs had a quasi‐spherical morphology and were completely transformed into soft bowl‐like nanocapsules in the simulated tumor microenvironment through the breakage of Mn−O bonds, which decreased their Young's modulus from 165.7 to 84.5 MPa. Due to their unique stiffness transformation properties, the MMONs had reduced macrophage internalization, improved tumor cell uptake, and enhanced penetration of multicellular spheroids. In addition, in vivo experiments showed that the MMONs displayed a 3.79‐ and 2.90‐fold decrease in non‐specific liver distribution and a 2.87‐ and 1.83‐fold increase in tumor accumulation compared to their soft and stiff counterparts, respectively. Furthermore, chlorin e6 (Ce6) modified MMONs had significantly improved photodynamic therapeutic effect. [ABSTRACT FROM AUTHOR]

Background: Nanomedicine offers great potentials for theranostic studies via providing higher efficacy and safety levels. This work aimed to develop and evaluate a new nanoplatform as a tumor theranostic probe. Results: Carboxyl-functionalized graphene oxide nanosheets (FGO) was well synthesized from graphite powder and then conjugated with folic acid to act as a targeted nano-probe. Full characterization and in vitro cytotoxicity evaluation were conducted; besides, in vivo bio-evaluation was attained via intrinsic radioiodination approach in both normal and tumor-bearing Albino mice. The results indicated that FGO as well as conjugated graphene oxide nanosheets (CGO) are comparatively non-toxic to normal cells even at higher concentrations. Pharmacokinetics of FGO and CGO showed intensive and selective uptake in the tumor sites where CGO showed high T/NT of 7.27 that was 4 folds of FGO at 1 h post injection. Additionally, radioiodinated-CGO (ICGO) had declared a superior prominence over the previously published tumor targeted GO radiotracers regarding the physicochemical properties pertaining ability and tumor accumulation behavior. Conclusions: In conclusion, ICGO can be used as a selective tumor targeting agent for cancer theranosis with aid of I-131 that has a maximum beta and gamma energies of 606.3 and 364.5 keV, respectively. [ABSTRACT FROM AUTHOR]

The development of responsive nanoplatforms based on the tumor microenvironment (TME) is critical for tumor diagnosis and treatment. Concentrating on a single TME‐responsive nanoplatform, however, may result in insufficient diagnostic accuracy and treatment efficacy. Herein, layered double‐hydroxides (LDHs) and rare earth nanomaterials (Er@Lu) were combined to create a triple TME‐responsive nanoplatform that was then modified with cypate (a fluorescent dye with strong absorbance) by a peptide chain and loaded with epigallocatechin gallate (EGCG), a chemotherapeutic drug. Multiple responses to TME occurred when Er@Lu/LDH‐EGCG reached the colorectal tumor region. Based on an acidic TME, the nanoplatform cracked and released Ni2+ and EGCG. NiS, which was produced by the reaction of Ni2+ with abundant H2S in tumor cells, was used for photothermal therapy and the released EGCG was used for chemotherapy. The MMP‐7 enzyme specifically expressed in tumor cells recognized and cut the peptide chain, resulting in cypate release. The fluorescence of the Er@Lu was then restored along with the release of cypate because of the absorption competition disappearance. Compared to a single TME response, Er@Lu/LDH‐EGCG with a triple TME response led to a better synergistic therapeutic effect in vitro and in vivo. This work has provided new approaches for developing multiple TME‐responsive therapeutic nanoplatforms for synergistic therapy with improved diagnosis and therapeutic efficiency. [ABSTRACT FROM AUTHOR]

Immunotherapy has achieved remarkable research outcomes and shows the potential to cure cancer. However, its therapeutic response is limited in terms of the immunosuppressive tumor microenvironment induced by hypoxia, in which the adenosinergic A2A receptor (A2AR) pathway is mainly participated. Here, we developed a novel core/shell structured nanoplatform composed of macrophage membrane-coated mesoporous silica nanoparticles which loaded catalase, doxorubicin (Dox), and resiquimod (R848), to promote the efficacy of immunotherapy. The nanoplatform is able to actively target the tumor site via ligand binding, and the A2AR of T regulatory (Treg) cells can further be blocked due to in situ oxygen production by hydrogen peroxide catalysis. Meanwhile, Dox and R848 released from the nanoplatform can induce immunogenic cell death and enhance the activation of dendritic cells (DCs), respectively. Thus, the improved microenvironment by A2AR blockade and the stimulation of the DCs to enhance the CD8+ T cells mediated immune response were achieved. Consequently, the expression of Treg cells decreased to 9.79% in tumor tissue and the inhibition rate of tumor growth reached 73.58%. Therefore, this nanoplatform provides a potential strategy for clinical application in cancer immunotherapy. Multifunctional nanoplatform inhibiting adenosine A2AR via in situ oxygen supply, inducing immunogenic cell death of tumor cells, and activating dendritic cells for enhanced immunotherapy. [Display omitted] • A nanoplatform composed of catalase, doxorubicin and resiquimod is developed. • Macrophage membrane-modified nanoplatform possesses better pharmacokinetics. • Suppressive TME is improved by blocking the A2AR via in situ oxygen production. • CD8+ T cell activation and Treg inhibition synergistically enhance immunotherapy. [ABSTRACT FROM AUTHOR]

After periodontal tissue injury, reconstruct soft tissue sealing around the tooth surface is of fundamental importance to treat periodontitis. Among multiple cell types, fibroblast plays a central role in reestablishing functional periodontium. To enhance fibroblast activity, a novel metal-organic framework-based nanoplatform is fabricated using mesoporous Prussian blue (MPB) nanoparticles to load baicalein (BA), named MPB-BA. Drug release test displayed sustained BA release of MPB-BA. Cell proliferation, transwell migration and wound healing tests revealed accelerated fibroblast proliferation and migration for the established MPBBA nanoplatform. Moreover, vinculin immunofluorescence staining, western blot and quantitative real-time PCR analysis showed up-regulated vinculin protein and integrin α5 and integrin β1 gene expressions for MPB-BA, suggesting improved cell adhesion. In addition, hematoxylin and eosin (H&E) and Masson trichromatic staining suggested superior anti-inflammatory and collagen fiber reconstruction effects for MPB-BA in a rat experimental periodontitis model in vivo. Our study may provide a promising strategy for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Abstract The acidic characteristic of the tumor site is one of the most well‐known features and provides a series of opportunities for cancer‐specific theranostic strategies. In this regard, pH‐responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI‐guided theranostic nanoplatforms for tumor‐specific treatments. Therefore, various MRI‐based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH‐responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH‐responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH‐responsiveness for cancer diagnosis and therapy are discussed.

Epitaxy is the process of crystallization of monocrystalline layers and nanostructures on a crystalline substrate. It allows for the crystallization of various semiconductor layers on a finite quantity of semiconductor substrates, like GaAs, InP, GaP, InGaP, GaP, and many others. The growth of epitaxial heterostructures is very complicated and requires special conditions and the precise control of the growth temperature, the pressure in the reactor, and the flow of the precursors. It is used to grow epitaxial structures in lasers, diodes, detectors, photovoltaic structures, and so on. Semiconductors themselves are not suitable materials for application in surface-enhanced Raman spectroscopy (SERS) due to poor plasmonic properties in the UV/VIS range caused by missing free electrons in the conduction band due to the existing band gap. A plasmonic material is added on top of the nanostructured pattern, allowing for the formation of mixed photon–plasmon modes called localized surface plasmon-polaritons which stand behind the SERS effect. Typically, gold and silver are used as functional plasmonic layers. Such materials could be deposited via chemical or physical process. Attention has also been devoted to other plasmonic materials, like ones based on the nitrides of metals. The SERS performance of a functional surface depends both on the response of the plasmonic material and the morphology of the underlying semiconductor epitaxial layer. In the context of SERS, epitaxial growth allows for the fabrication of substrates with well-defined 3D nanostructures and enhanced electromagnetic properties. In this work, we described the possible potential plasmonic modification, composed of various coatings such as noble metals, TiN, and others, of well-developed epitaxial nanostructures for the construction of a new type of highly active SERS platforms. This abstract also highlights the role of epitaxial growth in advancing SERS, focusing on its principles, methods, and impact. Furthermore, this work outlines the potential of epitaxial growth to push the boundaries of SERS. The ability to design substrates with tailored plasmonic properties opens avenues for ultralow concentration detection.

Photothermal therapy has the characteristics of minimal invasiveness, controllability, high efficiency, and strong specificity, which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. However, due to the limited tissue penetration of infrared light, it is difficult to promote and apply in clinical practice. The eye is the only transparent tissue in human, and infrared light can easily penetrate the eye tissue, so it is expected that photothermal therapy can be used to treat fundus diseases. Here in, a new nano-platform assembled by liposome and indocyanine green (ICG) was used to treat retinoblastoma. ICG was assembled in liposomes to overcome some problems of ICG itself. For example, ICG is easily quenched, self-aggregating and instability. Moreover, liposomes can prevent free ICG from being cleared through the systemic circulation. The construction of the nano-platform not only ensured the stability of ICG in vivo, but also realized imaging-guide photothermal therapy, which created a new strategy for the treatment of retinoblastoma.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Vaccination is an urgently needed and effective option to address epidemic, cancers, allergies, and other diseases. Nasal administration of vaccines offers many benefits over needle-based injection including high compliance and less risk of infection. Inactivated or attenuated vaccines as convention vaccine present potential risks of pathogenic virulence reversal, the focus of nasal vaccine development has shifted to the use of next-generation (subunit and nucleic acid) vaccines. However, subunit and nucleic acid vaccine intranasally have numerous challenges in development and utilization due to mucociliary clearance, mucosal epithelial tight junction, and enzyme/pH degradation. Nanoplatforms as ideal delivery systems, with the ability to enhance the retention, penetration, and uptake of nasal mucosa, shows great potential in improving immunogenic efficacy of nasal vaccine. This review provides an overview of delivery strategies for overcoming nasal barrier, including mucosal adhesion, mucus penetration, targeting of antigen presenting cells (APCs), enhancement of paracellular transportation. We discuss methods of enhancing antigen immunogenicity by nanoplatforms as immune-modulators or multi-antigen co-delivery. Meanwhile, we describe the application status and development prospect of nanoplatforms for nasal vaccine administration. Development of nanoplatforms for vaccine delivery via nasal route will facilitate large-scale and faster global vaccination, helping to address the threat of epidemics. [Display omitted] • The advantages and challenges of nasal vaccine delivery were described. • Design strategies for advanced nanoplatform of enhancing nasal vaccine delivery were discussed. • Co-delivery of adjuvants and multi-antigens enhanced vaccine immunogenicity. • The current application of nasal vaccines in disease prevention and treatment was summarized. • This review provided new inspiration for the further development of nasal vaccine. [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. Methods A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. Results The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. Conclusions Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC. Graphical Abstract

• Focusing on the clinical problems, the renal dual-targeting black phosphorus nanoplatform (BP@PEG-LTH-4OI) was designed for treating AKI. • BP@PEG-LTH-4OI promotes efferocytosis by clearing ROS to inhibit the progression of AKI. • The biological degradation triggered by ROS induces the release of 4OI, achieving sequential therapy for AKI. • Two AKI animal models have validated the outstanding therapeutic efficacy of BP@PEG-LTH-4OI. Efferocytosis, the clearance of apoptotic cells, is an essential process for resolving inflammation. Current evidence suggests that in acute kidney injury (AKI), the inflammatory cascade triggered by oxidative stress in damaged tissues can impair efferocytosis. This disrupts the clearance of apoptotic cells, exacerbates inflammatory reactions, and ultimately leads to tissue damage. To address this challenge, we developed a novel renal dual-targeting nanoplatform for AKI treatment based on black phosphorus nanosheets (BPNSs). Surface modification with LTH and 4-Octyl itaconate (4OI) endowed BPNSs with both renal tubulars targeting specificity and sustained antioxidant properties. This nanoplatform could effectively target damaged renal tubular epithelial cells, scavenge excess reactive oxygen species (ROS), alleviate oxidative stress, enhance efferocytosis, inhibit inflammatory responses, and ultimately achieve the specific therapeutic goal of AKI. [ABSTRACT FROM AUTHOR]

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft., (© 2024 Wiley‐VCH GmbH.)

Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer with disappointing treatment and high mortality. Tumor microenvironment (TME) plays an important role in the invasion and metastasis of TNBC through multiple complex processes. Most anti-metastatic therapies only focus on cancer cells themselves or interfering with single factors of the metastasis process, which is often related to poor outcomes. Thus, effective TNBC treatment relies on regulating multiple key metastasis-related aspects of the TME. Herein, a self-targeting Metal-Organic Frameworks (MOFs) nanoplatform (named as MTX-PEG@TPL@ZIF-8) was designed to improve treatment of TNBC through tumor microenvironment remodeling and chemotherapy potentiation. The self-targeting MOF nanoplatform is consist of ZIF-8 nanoparticles loaded triptolide (TPL) and followed by the coating with methotrexate-polyethylene glycol conjugates (MTX-PEG). Due to MTX's affinity for the overexpressed folate receptor on tumor cell surfaces, MTX-PEG@TPL@ZIF-8 enables effective accumulation and deep penetration in the tumor area by an MTX-mediated self-targeting strategy. This MOF nanoplatform could promptly release the medication after penetrating the tumor cell, due to pH-triggered degradation. Its anti-metastasis mechanism is to inhibit tumor invasion and metastasis by down-regulating the expression of Vimentin, MMP-2 and MMP-9 and increasing the expression of E-cadherin, upregulation of cleaved caspase-3 and cleaved caspase-9 protein expression promote the apoptosis of tumor cells, thereby reducing their migration. It also downregulated the expression of VEGF and CD31 protein to inhibit the generation of neovascularization. Overall, these findings suggest the self-targeting MOF nanoplatform offers new insights into the treatment of metastatic TNBC by TME remodeling and potentiating chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles ( e.g. , nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino)ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Xu, Zhao, Sun, Xu and Li.)

A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders., Competing Interests: The authors assert that the research was carried out without any commercial or financial affiliations that could be perceived as a possible conflict of interest. Fig. 6A is created using Figdraw (www.figdraw.com)., (© 2024 The Authors.)