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Abstract3-D multi-faceted, nano-globular PAMAM dendritic skeleton is a highly significant polymer that offers applications in biomedical, industrial, environmental and agricultural fields. This is mainly due to its enhanced properties, including adjustable surface functionalities, biocompatibility, non-toxicity, high uniformity and reduced cytotoxicity, as well as its numerous internal cavities. This trait inspires further exploration and advancements in tailoring approaches. The implementation of deliberate strategic modifications in the morphological characteristics of PAMAM is crucial through chemical and biological interventions, in addition to its therapeutic advancements. Thus, the production of peripheral groups remains a prominent and highly advanced technique in molecular fabrication, aimed at boosting the potential of PAMAM conjugates. Currently, there exist numerous dendritic-hybrid materials, despite the widespread use of PAMAM-conjugated frameworks as drug delivery systems, which are well regarded for their efficacy in enhancing potency through the incorporation of surface functions. This paper provides a comprehensive review of recent progress in the design and assembly of various components of PAMAM conjugates, focusing on their unique formulations. The review encompasses synthetic methodologies, a thorough evaluation of their applicability, and an analysis of their potential functions in the context of Drug Delivery Systems (DDS) in the current period. [ABSTRACT FROM AUTHOR]

Nasopharyngeal cancer (NPC) is a challenging malignancy with a poor prognosis due to late diagnosis and resistance to conventional treatments. Nanotechnology offers promising solutions to address these limitations by enabling targeted drug delivery, enhancing therapeutic efficacy, and facilitating multimodal treatment strategies. By leveraging the unique properties of nanomaterials and nanocarrier systems, innovative approaches for early detection, targeted treatment, and multimodal therapy can be developed, paving the way for more effective and personalized management of NPC. This review provides a comprehensive overview of recent developments and applications of nanotechnology in NPC therapy, focusing on improving drug stability, biodistribution, and targeted delivery to NPC tumors. [ABSTRACT FROM AUTHOR]

Among the numerous driving forces that cause the atherosclerotic cardiovascular disease (ASCVD), pathogenic bacterial extracellular membrane nanovesicles (BEMNs) containing toxins and virulence factors appear to be the key trigger of inflammation and atherogenesis, the major processes involved in the pathogenesis of ASCVD. Since BEMNs are the carriers of nanosized biomolecules to distant sites, they are now being considered as a novel drug delivery system. Nowadays, many therapeutic strategies are used to treat ASCVD. However, the conventional anti-atherosclerotic therapies are not effective enough. This primarily due to the inefficiency of non-targeted drug delivery systems to tissue affected areas, which, in turn, leads to numerous side effects, as well as faulty pharmacokinetics. In this regard, nanomedicine methods using nanoparticles (NPs) as targeted drug delivery vehicles proved to be extremely useful. Bioengineered BEMNs equipped with disease-specific ligand moieties and loaded with corresponding drugs represent a promising tool in nanomedicine, which can be used as a novel drug delivery system for a successful therapy of ASCVD. In this review, we outline the involvement of pathogenic BEMNs in the triggering of ASCVD, the conventional therapeutic strategies for the treatment of ASCVD, and the recent trends in nanomedicine using BEMNs and NPs as a vehicle for targeted drug delivery. [ABSTRACT FROM AUTHOR]

Nanotheranostics, an amalgamation of therapeutic and diagnostic capabilities at the nanoscale, is revolutionizing personalized medicine. Polymer-drug conjugates (PDCs) stand at the forefront of this arena, offering a multifaceted approach to treat complex diseases such as cancer. This review explores the recent advancements in PDCs, highlighting their design principles, working mechanisms, and the therapeutic applications. We discuss the incorporation of imaging agents into PDCs that allow for real-time monitoring of drug delivery and treatment efficacy. With the aim of improving patient care, the review examines how PDCs enable targeted drug delivery, minimize side effects, and provide valuable diagnostic data, hence enhancing the precision of medical interventions. We also address the challenges facing the clinical translation of PDCs, such as scalability, regulatory hurdles, and cost-effectiveness, providing a comprehensive outlook on the future of nanotheranostics in patient management. [ABSTRACT FROM AUTHOR]

In order to improve the delivery performance of curcumin (CUR) in liver cancer cells, we prepared a targeted and reduction‐sensitive prodrug, folic acid‐polyethylene glycol‐disulfide bond‐curcumin (FA‐PEG‐SS‐CUR). The synthesis involved the conjugation of CUR with NH2‐PEG‐NH2 through a disulfide bond, followed by the connection of CUR‐SS‐PEG‐NH2 to FA‐COOH via acylation. The resultant FA‐PEG‐SS‐CUR prodrug self‐assembled into nano micelles in aqueous solutions, displaying excellent dispersibility with an approximate particle size of 119 nm. In vitro drug release studies demonstrated the sensitivity of FA‐PEG‐SS‐CUR to glutathione (GSH), displaying sustained release performance. After 72 h, FA‐PEG‐SS‐CUR exhibited a drug release rate of 38% at low GSH concentration and 59% at high GSH concentration. Notably, FA‐PEG‐SS‐CUR micelles exhibited favorable biocompatibility. The hemolysis rate resulting from co‐incubation with red blood cells remained below 3%. Furthermore, cytotoxicity experiments unveiled the substantial cytotoxicity of FA‐PEG‐SS‐CUR micelles against HepG2 tumor cells. Cellular uptake studies confirmed the greater internalization of FA‐PEG‐SS‐CUR by HepG2 cells compared to the non‐targeted PEG‐SS‐CUR. The findings highlight the potential of FA‐PEG‐SS‐CUR as an ideal drug delivery system for CUR due to its facile synthesis and strong self‐assembly performance. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) is currently the main method for treating coronary artery stenosis, but the incidence of restenosis after PCI is relatively high. Restenosis, the narrowing of blood vessels by more than 50% of the normal diameter after PCI, severely compromises the therapeutic efficacy. Therefore, preventing postinterventional restenosis is important. Vascular restenosis is mainly associated with endothelial injury, the inflammatory response, the proliferation and migration of vascular smooth muscle cells (VSMCs), excessive deposition of extracellular matrix (ECM) and intimal hyperplasia (IH) and is usually prevented by administering antiproliferative or anti-inflammatory drugs through drug-eluting stents (DESs); however, DESs can lead to uncontrolled drug release. In addition, as extracorporeal implants, they can cause inflammation and thrombosis, resulting in suboptimal treatment. Therefore, there is an urgent need for a drug carrier with controlled drug release and high biocompatibility for in vivo drug delivery to prevent restenosis. The development of nanotechnology has enabled the preparation of nanoparticle drug carriers with low toxicity, high drug loading, high biocompatibility, precise targeting, controlled drug release and excellent intracellular delivery ability. This review summarizes the advantages of nanoparticle drug carriers for treating vascular restenosis, as well as how nanoparticles have improved targeting, slowed the release of therapeutic agents, and prolonged circulation in vivo to prevent vascular restenosis more effectively. The overall purpose of this review is to present an overview of nanoparticle therapy for vascular restenosis. We expect these findings to provide insight into nanoparticle-based therapeutic approaches for vascular restenosis. [ABSTRACT FROM AUTHOR]

Targeted drug delivery for primary brain tumors, particularly gliomas, is currently a promising approach to reduce patient relapse rates. The use of substitutable scaffolds, which enable the sustained release of clinically relevant doses of anticancer medications, offers the potential to decrease the toxic burden on the patient's organism while also enhancing their quality of life and overall survival. Upconversion nanoparticles (UCNPs) are being actively explored as promising agents for detection and monitoring of tumor growth, and as therapeutic agents that can provide isolated therapeutic effects and enhance standard chemotherapy. Our study is focused on the feasibility of constructing scaffolds using methacrylated hyaluronic acid with additional impregnation of UCNPs and the chemotherapeutic drug temozolomide (TMZ) for glioma treatment. The designed scaffolds have been demonstrated their efficacy as a drug and UCNPs delivery system for gliomas. Using the aggressive orthotopic glioma model in vivo , it was found that the scaffolds possess the capacity to ameliorate neurological disorders in mice. Moreover, upon intracranial co-implantation of the scaffolds and glioma cells, the constructs disintegrate into distinct segments, augmenting the release of UCNPs into the surrounding tissue and concurrently reducing postoperative damage to brain tissue. The use of TMZ in the scaffold composition contributed to restraining glioma development and the reduction of tumor invasiveness. Our findings unveil promising prospects for the application of photopolymerizable biocompatible scaffolds in the realm of neuro-oncology. [ABSTRACT FROM AUTHOR]

Materials data science and machine learning (ML) are pivotal in advancing cancer treatment strategies beyond traditional methods like chemotherapy. Nanotherapeutics, which merge nanotechnology with targeted drug delivery, exemplify this advancement by offering improved precision and reduced side effects in cancer therapy. The development of these nanotherapeutic agents depends critically on understanding nanoparticle (NP) properties and their biological interactions, often analyzed through molecular dynamics (MD) simulations. This study enhances these analyses by integrating ML with MD simulations, significantly improving both prediction accuracy and computational efficiency. We introduce a comprehensive three-stage methodology for predicting the solvent-accessible surface area (SASA) of NPs, which is crucial for their therapeutic efficacy. The process involves training an ML model to forecast the many-body tensor representation (MBTR) for future time steps, applying data augmentation to increase dataset realism, and refining the SASA predictor with both augmented and original data. Results demonstrate that our methodology can predict SASA values 299 time steps ahead with a 40-fold speed improvement and a 25% accuracy increase over existing methods. Importantly, it provides a 300-fold increase in computational speed compared to traditional simulation techniques, offering substantial cost and time savings for nanotherapeutic research and development. [ABSTRACT FROM AUTHOR]

Over the years, nanotechnology has gained popularity as a viable solution to address gene and drug delivery challenges over conventional methods. Extensive research has been conducted on nanosystems that consist of organic/inorganic materials, drugs, and its biocompatibility become the primary goal of improving drug delivery. Various surface modification methods help focus targeted and controlled drug release, further enabling multidrug delivery also. This newer technology ensures the stability of drugs that can unravel the mechanisms involved in cellular processes of disease development and its management. Tailored medication delivery provides benefits such as therapy, controlled release, and reduced adverse effects, which are especially important for controlling illnesses like cancer. However, multifunctional nanocarriers that possess high viscoelasticity, extended circulation half-life, biocompatibility, and biodegradability face some challenges and limitations too in human bodies. To produce a consistent therapeutic platform based on complex three-dimensional nanoparticles, careful design and engineering, thorough orthogonal analysis methods, and reproducible scale-up and manufacturing processes will be required in the future. Safety and effectiveness of nano-based drug delivery should be thoroughly investigated in preclinical and clinical trials, especially when considering biodistribution, targeting specific areas, and potential immunological toxicities. Overall, the current review article explores the advancements in nanotechnology, specific to nanomaterial-enabled drug delivery systems, carrier fabrication techniques and modifications, disease management, clinical research, applications, limitations, and future challenges. The work portrays how nanomedicine distribution affects healthcare with an emphasis on the developments in drug delivery techniques. [ABSTRACT FROM AUTHOR]

Cancer is a multifaceted disease characterized by the gradual accumulation of genetic and epigenetic alterations within cells, leading to uncontrolled cell growth and invasive behavior. The intricate interplay between environmental factors, such as exposure to carcinogens, and the molecular cascades governing cell growth, differentiation, and survival contributes to cancer's development and progression. This review offers a comprehensive overview of key molecular targets and their roles in cancer development. Peroxisome proliferator-activated receptors are implicated in various cancers due to their role in regulating lipid metabolism, inflammation, and cell proliferation. Nuclear factor erythroid 2-related factor 2 protects cells from oxidative damage but can also promote tumor cell survival. Cytochrome P450 1B1 metabolizes exogenous and endogenous substances, and its increased expression is observed in several cancers. The constitutive androstane receptor regulates gene expression, and its dysregulation can lead to liver cancer. Transforming growth factor-beta 2 is involved in the development and progression of various cancers by dysregulating cell proliferation, differentiation, and migration. Chelation treatment has been investigated for removing heavy metals, while genetically altered immune cells show promise in treating specific cancers. Metal–organic frameworks and fibronectin targeting represent new directions in cancer treatment. While some heavy metals, such as arsenic, chromium, nickel, and cadmium, are known to have carcinogenic properties, others, like zinc, Copper, gold, bismuth, and silver, have many uses that highlight their potential as effective cancer control tactics. There are a variety of heavy metal-based technologies that show potential for improving cancer treatment methods, including targeted drug delivery, improved radiation, and diagnostic tools. [ABSTRACT FROM AUTHOR]

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body's immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients' quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity. [ABSTRACT FROM AUTHOR]

To minimize off-target adverse effects and improve drug efficacy, various tissue-specific drug delivery systems have been developed. However, even in diseased organs, both normal and stressed, dying cells coexist, and a targeted delivery system specifically for dying cells has yet to be explored to mitigate off-target effects within the same organ. This study aimed to establish such a system. By examining the surfaces of dying cells in vitro, we identified P-selectin glycoprotein ligand-1 (PSGL-1) as a universal marker for dying cells, positioning it as a potential target for selective drug delivery. We demonstrated that liposomes conjugated with the PSGL-1 binding protein P-selectin had significantly greater binding efficiency to dying cells compared to control proteins such as E-selectin, L-selectin, galectin-1, and C-type lectin-like receptor 2. Using thioacetamide (TAA) to induce hepatitis and hepatocyte damage in mice, we assessed the effectiveness of our P-selectin-based delivery system. In vivo, P-selectin-conjugated liposomes effectively delivered fluorescent dye and the apoptosis inhibitor z-DEVD to TAA-damaged livers in wild-type mice, but not in PSGL-1 knockout mice. In TAA-treated wild-type mice, unconjugated liposomes required a 100-fold higher z-DEVD dose compared to P-selectin-conjugated liposomes to achieve a comparable, albeit less effective, therapeutic outcome in lowering plasma alanine transaminase levels and alleviating thrombocytopenia. This emphasizes that P-selectin conjugation enhances drug delivery efficiency by approximately 100-fold in mice. These results suggest that P-selectin-based liposomes could be a promising strategy for targeted drug delivery, enabling both diagnosis and treatment by specifically delivering cell-labeling agents and rescue agents to dying cells via the P-selectin–PSGL-1 axis at the individual cell level. [ABSTRACT FROM AUTHOR]

Cysteine cathepsins are a fascinating group of proteolytic enzymes that play diverse and crucial roles in numerous biological processes, both in health and disease. Understanding these proteases is essential for uncovering novel insights into the underlying mechanisms of a wide range of disorders, such as cancer. Cysteine cathepsins influence cancer biology by participating in processes such as extracellular matrix degradation, angiogenesis, immune evasion, and apoptosis. In this comprehensive review, we explore foundational research that illuminates the diverse and intricate roles of cysteine cathepsins as diagnostic markers and therapeutic targets for cancer. This review aims to provide valuable insights into the clinical relevance of cysteine cathepsins and explore their capacity to advance personalised and targeted medical interventions in oncology. • Cysteine cathepsins are pivotal in many cancer processes, making them desirable therapeutic targets. • Irregular cysteine cathepsin levels can serve as diagnostic and prognostic biomarkers in various cancers. • Development of molecular probes for cysteine cathepsins enhances diagnostic imaging and image-guided surgery. • Selective inhibitors and novel drug delivery systems targeting cysteine cathepsins hold promise for innovative cancer treatments. • Advances in antibody-drug conjugates utilizing cysteine cathepsins offer major potential in cancer treatment. [ABSTRACT FROM AUTHOR]

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applications in bone tissue engineering, advanced imaging techniques, and targeted drug delivery. For diagnosis, NPs enhance imaging contrast and sensitivity by integrating targeting ligands, which significantly improve the specific recognition and localization of tumor cells for early detection. For treatment, NPs enable targeted drug delivery, increasing drug accumulation at tumor sites while reducing systemic toxicity. In conclusion, understanding bone microenvironment and using the unique properties of NPs holds great promise in improving disease management, enhancing treatment outcomes, and ultimately improving the quality of life for patients with malignant bone tumors. Further research and development will undoubtedly contribute to the advancement of personalized medicine in the field of bone oncology. [ABSTRACT FROM AUTHOR]

Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia‐inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel–Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen‐dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management. [ABSTRACT FROM AUTHOR]

Aim: To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. Methods: Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. Results: SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of −23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. Conclusion: SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity. [ABSTRACT FROM AUTHOR]

Metastatic ovarian cancer (MOC) is highly deadly, due in part to the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent cancer cells. Here, we demonstrated the effectiveness of a combination therapy of GRP78-targeted (TNPGRP78pep) and non-targeted (NP) nanoparticles to deliver a novel DM1-prodrug to MOC in a syngeneic mouse model. Cell surface-GRP78 is overexpressed in MOC, making GRP78 an optimal target for selective delivery of nanoparticles to MOC. The NP + TNPGRP78pep combination treatment reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The NP and TNPGRP78pep components functioned synergistically through two proposed mechanisms of action. The TNPGRP78pep targeted non-adherent cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the NP passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment. [Display omitted] • Traditional chemotherapies show limited efficacy against metastatic ovarian cancer. • Novel DM1-prodrug loaded nanoparticles provide improved therapeutic index. • Combo of targeted and non-targeted nanoparticles treated metastatic ovarian cancer. • Two synergistic mechanisms of action for non-targeted versus targeted nanoparticles. • Antitumor immune involvement; increased T cells and macrophages in treated groups. [ABSTRACT FROM AUTHOR]

Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvβ3 and gets continuously activated by apoptosis. TPD1 facilitates the caspase-3-mediated in situ amplification that results in tumor-specific accumulation of doxorubicin. This local concentration of doxorubicin induces immunogenic cell death and promotes the recruitment of immune cells to the tumor site. Notably, the tumor-targeting capabilities of TPD1 help bypass the systemic immunotoxicity of doxorubicin. Consequently, this alters the tumor microenvironment, converting it into a 'hot' tumor that is more susceptible to immune checkpoint inhibition. We demonstrated the anti-metastatic and anti-cancer efficacy of this treatment using various xenograft and metastatic models. This study underscores the high potential of caspase-3 cleavable peptide-drug conjugates to be used in conjunction with anti-cancer immunotherapies. Metastatic TNBC targeting strategy of TPD1 utilizing focused immune stimulation and caspase-3 mediated amplification cycle. [Display omitted] • Demonstrated effective induction of immunogenic cell death and enhanced immunogenicity in tumors. • Achieved effective targeted drug delivery utilizing the caspase-3 mediated activating cycle. • Successfully targets both primary tumors and metastasis in diverse mice TNBC models. • Shows synergistic anticancer efficacy when combined with anti-PD1 treatments. • Exhibits minimal immunotoxic effects compared to doxorubicin, ensuring safer combination therapies. [ABSTRACT FROM AUTHOR]

This study revolves around the synthesis of poly (amino acid)-based polymers, specifically designed as block copolymers incorporating poly (glutamic acid) and poly (ethylene glycol), with varying glutamic acid moieties. Extensive characterization of these block copolymers was carried out using Fourier Transform Infrared and proton nuclear magnetic resonance (1H NMR) spectroscopy. The integration of the potent anti-cancer agent, doxorubicin, into these constructs was successfully achieved. The determination of nanoparticle sizes was accomplished through dynamic laser light scattering; while, zeta potential measurements provided insights into surface charges. Following the drug loading into nanomicelles, the release profiles were investigated under conditions simulating the tumor-specific acidic pH and physiological blood pH (7.4). In vitro cytotoxicity evaluations were performed, revealing dose and time-dependent reactions for both free and loaded doxorubicin against the MCF-7 breast cancer cell line. Additionally, the mechanisms of cellular uptake were explored using confocal laser scanning microscopy and flow cytometry. The findings unveiled that the cellular uptake of free doxorubicin predominantly follows a diffusion process; while, the drug loaded within nanoparticles is internalized via endocytosis. The nanoparticles were skillfully engineered to possess optimal size, shape, and surface charge, thereby showcasing their potential as proficient vehicles for targeted drug delivery. In summary, this study not only demonstrates the successful synthesis and meticulous characterization of poly (amino acid)-based nanocarriers but also underscores their biocompatibility, favorable attributes, and promising capabilities as effective platforms for precise and targeted drug delivery. [ABSTRACT FROM AUTHOR]

Lanthanide luminescent materials have rapidly emerged as potential candidates in the fields of drug delivery and bioimaging. In this study a spherical composite material theory with uniform particle size, good biocompatibility, fluorescence emission performance and an efficient targeted drug delivery system was proposed. To achieve this, a facile ultrasonic atomization approach to synthesize sodium alginate-lanthanum (SA-La) cross-linked microspheres at room temperature was developed, and then they were loaded with doxorubicin (DOX), yielding DOX@SA-La for targeted liver cancer cell treatment. Fluorescence studies indicated that the SA-La microspheres exhibited excellent fluorescence properties with intense blue fluorescence emitted. Moreover, the ability of drug release in-vitro of the SA-La and Calcium alginate (SA-Ca) microspheres were proved by UV-visible spectrophotometry, and the drug release values of these two drug carriers were considerable. In addition, cytotoxicity tests via the CCK-8 assay revealed that the DOX@SA-La delivery system considerably inhibited hepatocellular carcinoma cells growth. Conclusively, the SA-La fluorescent microsphere drug carriers enables real-time anti-cancer efficacy observations and analyses, having promise as a potent therapeutic and diagnostic tool for liver cancer treatments and drug tracing in the tumors. [ABSTRACT FROM AUTHOR]

Scientific research in recent decades has affirmed an increase in cancer incidence as a cause of death globally. Cancer can be considered a plurality of various diseases rather than a single disease, which can be a multifaceted problem. Hence, cancer therapy techniques acquired more accelerated and urgent approvals compared to other therapeutic approaches. Radiotherapy, chemotherapy, immunotherapy, and surgery have been widely adopted as routine cancer treatment strategies to suppress disease progression and metastasis. These therapeutic approaches have lengthened the longevity of countless cancer patients. Nonetheless, some inherent limitations have restricted their application, including insignificant therapeutic efficacy, toxicity, negligible targeting, non‐specific distribution, and multidrug resistance. The development of therapeutic oligomer nanoconstructs with the advantages of chemical solid‐phase synthesis, programmable design, and precise adjustment is crucial for advancing smart targeted drug nanocarriers. This review focuses on the significance of the different aptamer‐assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery. We discuss recent advancements in the design and utilization of aptamer‐tethered nanostructures to enhance the efficacy of cancer treatment. Valuably, this comprehensive review highlights self‐assembled aptamers as the exceptionally intelligent nano‐biomaterials for targeted drug delivery based on their superior stability, high specificity, excellent recoverability, inherent biocompatibility, and versatile functions. [ABSTRACT FROM AUTHOR]

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV). Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection. Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis. Article highlights A HIF-1α siRNA-loaded PLGA@lipid hybrid nanoparticles system was designed. An MSC-mediated biodegradable hybrid nanoparticle system for targeted delivery of HIF-1α siRNA was developed. The MSC-mediated homing enabled targeted ocular angiogenesis. MSCs can be potentially exploited as an ideal drug delivery system, a so-called Trojan horse strategy. Systemic administration of MSCs loaded with nanoparticles inhibited pathological angiogenesis. Integration of advanced nanomaterials with cell-based platforms can amplify the overall therapeutic impact. MSCs can be safely delivered without triggering a major immune reaction. The ability of MSCs to specifically migrate to CNV without accrual in other organs. [ABSTRACT FROM AUTHOR]

In this study, a red seaweed (Solieria robusta) containing ι‐carrageenan (Carr) was used for nanoparticles (NPs) synthesis using silver (Ag) ions. Initially, the ι‐Carr was extracted from S. robusta using the alkali method. The Carr extracted was fractionated into 3 fractions and > 14 kDa fraction showing high yield with maximum sulfate content characterized using Fourier transform infrared (FT‐IR) as ι‐Carr was used for AgNPs synthesis. The synthesized CarrAgNPs were again used for curcumin (Cur) encapsulation. The cytotoxicity of Carr, Cur, CarrAgNPs, and CurCarrAgNPs was evaluated using HeLa cell lines by MTT assay. The CarrAgNPs and CurCarrAgNPs were characterized using UV‐visible spectroscopy, as well as FT‐IR and XRD analysis. The UV‐visible spectrum confirms the CarrAgNPs showing characteristic SPR bands recorded between 344 and 490 nm with broad peak at 430 nm. The shape of the NPs is spherical, arranged in order of seven per chain. The XRD and FT‐IR characteristics confirm the orthorhombic crystal structure of these NPs. Remarkably, Cur‐loaded CarrAgNPs demonstrate potent anticancer properties by maximum reduction of HeLa cell viability after 24 h at 200 μg/mL in pH 7.4 in an MTT assay medium. A significant increase in the cancer cell viability was recorded at high concentrations of CurCarrAgNPs, confirming its less diffusion and dissolution properties and bioavailability due to lipophilic Cur encapsulation, whereas cytotoxicity was increased proportionately by increasing concentrations of Cur, Carr, and CarrAgNPs that confirm a direct relation with size, dissolution, and bioavailability recorded on the basis of cell death in 24 h of introduction at pH 7.4. The cytotoxicity results suggest the potential of Cur, Carr, CarrAgNPs, and CurCarrAgNPs for drug delivery in selective biomedical product developments. This study highlights the versatility and effectiveness of CurCarrAgNPs in cancer therapy by enhancing the efficacy of therapeutic interventions and targeted drug delivery. [ABSTRACT FROM AUTHOR]

Supramolecular assemblies of stimuli-responsive amphiphilic molecules have been of utmost interest in targeted drug delivery applications, owing to their capability of sequestering drug molecules in one set of conditions and releasing them in another. To minimize undesired disassembly and stabilize noncovalently encapsulated drug molecules, the strategy of core or shell cross-linking has become a fascinating approach to constructing cross-linked polymeric or small molecule-based nanoassemblies. In this article, we discuss the design and synthetic strategies for cross-linked nanoassemblies from small molecule-based amphiphiles, with robust stability and enhanced drug encapsulation capability. We highlight their potential biomedical applications, particularly in drug or gene delivery, and cell imaging. This feature article offers a comprehensive overview of the recent developments in the application of small molecule-based covalently cross-linked nanocarriers for materials and biomedical applications, which may inspire the use of these materials as a potential drug delivery system for future chemotherapeutic applications. [ABSTRACT FROM AUTHOR]

Targeted immunotherapies make substantial strides in clinical cancer care due to their ability to counteract the tumor's capacity to suppress immune responses. Advances in biomimetic technology with minimally immunogenic and highly targeted, are addressing issues of targeted drug delivery and disrupting the tumor's immunosuppressive environment to trigger immune activation. Specifically, the use of dendritic cell (DC) membranes to coat nanoparticles ensures targeted delivery due to DC's unique ability to activate naive T cells, spotlighting their role in immunotherapy aimed at disrupting the tumor microenvironment. The potential of DC's biomimetic membrane to mediate immune activation and target tumors is gaining momentum, enhancing the effectiveness of cancer treatments in conjunction with other immune responses. This review delves into the methodologies behind crafting DC membranes and the fusion of dendritic and tumor cell membranes for encapsulating therapeutic nanoparticles. It explores their applications and recent advancements in combating cancer, offering an all-encompassing perspective on DC biomimetic nanosystems, immunotherapy driven by antigen presentation, and the collaborative efforts of drug delivery in chemotherapy and photodynamic therapies. Current evidence shows promise in augmenting combined therapeutic approaches for cancer treatment and holds translational potential for various cancer treatments in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Diabetic atherosclerosis is one of the main causes of morbidity and mortality worldwide, but its therapeutic options are limited. Liraglutide (LIR), a synthetic analog of GLP-1 approved as an anti-obesity drug by the FDA, has been reported as a promising drug for diabetic atherosclerosis. However, the main problem with LIR is its use that requires regular parenteral injections, which necessitates the improvement of drug delivery for increased efficiency and minimization of injection numbers. Results: The objective of our present study was to prepare and characterize nanoparticles (BSA@LIR-PMF) for targeted drug delivery using LIR-encapsulated platelet membrane fragments (PMF) coated bovine serum albumin (BSA). We used various methods to characterize the prepared nanoparticles and evaluated their efficiency on diabetes-induced atherosclerosis in vitro and in vivo. The results showed that the nanoparticles were spherical and had good stability and uniform size with intact membrane protein structure. The loading and encapsulation rates (LR and ER) of BSA@LIR-PMF were respectively 8.29% and 90.39%, while the cumulative release rate was around 77.06% after 24 h. Besides, we also examined the impact of BSA@LIR-PMF on the proliferation, migration, phagocytosis, reactive oxygen species (ROS) levels, oxidative phosphorylation, glycolysis, lactate and ATP levels, and lipid deposition in the aortas. The results indicated that BSA@LIR-PMF could effectively inhibit ox-LDL-stimulated abnormal cell proliferation and migration, reduce the level of ROS and lactate concentration, and enhance the level of ATP, thereby improving oxidative phosphorylation in ox-LDL-treated cells. Conclusion: BSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis. It was anticipated that the BSA@LIR-PMF nanoparticles might be used for treating diabetes-associated cardiovascular complications. [ABSTRACT FROM AUTHOR]

Lung cancer has become the leading cause of cancer‐related deaths, surpassing all other forms of cancer. Among lung cancers, non‐small cell lung cancer (NSCLC) accounts for approximately 85% of cases. The use of tobacco, genetic traits, and radiation exposure are amongst the major reasons of lung cancer. The ongoing research in the medical field has considered the efficacy of nanocarriers in targeting various cancer cells. Among several biomaterials, lipid‐based nanocarriers have gained special attention due to their excellent compatibility, improved targeting efficacy, and encapsulation ability of diverse therapeutic agents. Phospholipids are naturally occurring amphiphilic moieties found in all living creatures. The presence of phospholipids in biomembrane aids the permeability of phospholipid‐based drug carrier. It can also facilitate targeting of therapeutic agents to cancer microenvironment without degrading the encapsulated drug. Phospholipids can be employed to develop conjugated nanocarriers and vesicular nanoformulation that can result in prolonged circulatory half‐life and controlled release of drugs. Phospholipids are also suitable biomaterials to attach a ligand for tissue‐specific targeting. Recent researches have reported effective targeting of chemotherapeutic agents, genes, and vaccines through phospholipid‐based nanocarriers to lung cancer cells. This review focuses on the rationality and applications of phospholipid‐based nanocarriers in lung cancer therapy. [ABSTRACT FROM AUTHOR]

As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment. [ABSTRACT FROM AUTHOR]

Enzymatic nanomotors harvest kinetic energy through the catalysis of chemical fuels. When a drop containing nanomotors is placed in a fuel-rich environment, they assemble into ordered groups and exhibit intriguing collective behaviour akin to the bioconvection of aerobic microorganismal suspensions. This collective behaviour presents numerous advantages compared to individual nanomotors, including expanded coverage and prolonged propulsion duration. However, the physical mechanisms underlying the collective motion have yet to be fully elucidated. Our study investigates the formation of enzymatic swarms using experimental analysis and computational modelling. We show that the directional movement of enzymatic nanomotor swarms is due to their solutal buoyancy. We investigate various factors that impact the movement of nanomotor swarms, such as particle concentration, fuel concentration, fuel viscosity, and vertical confinement. We examine the effects of these factors on swarm self-organization to gain a deeper understanding. In addition, the urease catalysis reaction produces ammonia and carbon dioxide, accelerating the directional movement of active swarms in urea compared with passive ones in the same conditions. The numerical analysis agrees with the experimental findings. Our findings are crucial for the potential biomedical applications of enzymatic nanomotor swarms, ranging from enhanced diffusion in bio-fluids and targeted delivery to cancer therapy. Enzymatic nanomotors exhibit collective behaviour in fuel-rich environments, forming swarms with enhanced propulsion and coverage. This study investigates the factors affecting swarm movement, revealing that solutal buoyancy drives their motion, with potential biomedical applications like targeted drug delivery. [ABSTRACT FROM AUTHOR]

Drug-carrying nanoparticles can be recognized and captured by macrophages and cleared away by the immune system, resulting in reduced drug efficacy and representing the main drawbacks. Biomimetic nanoparticles, which are coated with cell membranes from natural resources, have been applied to address this problem. This type of nanoparticle maintains some specific biological activities, allowing them to carry drugs reaching designated tissues effectively and have a longer time in circulation. This review article aims to summarize recent progress on biomimetic nanoparticles based on cell membranes. In this paper, we have introduced the classification of biomimetic nanoparticles, their preparation and characterization, and their applications in inflammatory diseases and malignant tumors. We have also analyzed the shortcomings and prospects of this technology, hoping to provide some clues for basic researchers and clinicians engaged in this field. [ABSTRACT FROM AUTHOR]

Lung cancer is frequently detected in an advanced stage and has an unfavourable prognosis. Conventional therapies are ineffective for the treatment of metastatic lung cancer. While certain molecular targets have been identified as having a positive response, the absence of appropriate drug carriers prevents their effective utilization. Lung cancer cell-derived exosomes (LCCDEs) have gained attention for their involvement in the development of cancer, as well as their potential for use in diagnosing, treating, and predicting the outcome of lung cancer. This is due to their biological roles and their inherent ability to transport biomolecules from the donor cells. Lung cancer-associated cell-derived extracellular vesicles (LCCDEVs) have the ability to enhance cell proliferation and metastasis, influence angiogenesis, regulate immune responses against tumours during the development of lung cancer, control drug resistance in lung cancer treatment, and are increasingly recognised as a crucial element in liquid biopsy evaluations for the detection of lung cancer. Therapeutic exosomes, which possess inherent intercellular communication capabilities, are increasingly recognised as effective vehicles for targeted drug delivery in precision medicine for tumours. This is due to their exceptional biocompatibility, minimal immunogenicity, low toxicity, prolonged circulation in the bloodstream, biodegradability, and ability to traverse different biological barriers. Currently, multiple studies are being conducted to create new means of diagnosing and predicting outcomes using LCCDEs, as well as to develop techniques for utilizing exosomes as effective carriers for medication delivery. This paper provides an overview of the current state of lung cancer and the wide range of applications of LCCDEs. The encouraging findings and technologies suggest that the utilization of LCCDEs holds promise for the clinical treatment of lung cancer patients. [ABSTRACT FROM AUTHOR]

Nanoparticulate delivery systems have been attracting attention in pharmaceutical sciences for enhanced drug bioavailability and targeted delivery. Specifically, these systems can enhance the solubility of poorly water-soluble drugs, protect therapeutic agents from degradation, prolong circulation time in the body, control drug release, and facilitate the precise targeting of drugs to specific tissues or cells. However, once administered into the body, nanoparticles often encounter significant challenges that can affect their efficacy and safety, such as issues with stability, biocompatibility, and targeting. The surface properties of nanoparticles are one of the most important features as they can greatly influence the interactions between nanoparticles themselves and between nanoparticles and biological targets. Key surface characteristics, such as charge, hydrophobicity, and the presence of functional groups, determine how nanoparticles behave in biological environments, thereby influencing their stability, cellular uptake, and ability to avoid immune clearance. Modification of the nanoparticle surface has been shown to be an effective approach to modulate the physicochemical and biological properties of nanoparticles, achieving desired therapeutic efficacy in vivo. This review aims to summarize recent advances in surface decoration of nanoparticles, with an emphasis on improved colloidal and biological stability, reduced toxicity, and enhanced drug targeting. The challenges and future perspectives of nanoparticle surface modification approaches are also discussed. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is one of the deadliest gynecological malignancies in the world and is the leading cause of cancer-related death in women. The complexity and difficult-to-treat nature of OC pose a huge challenge to the treatment of the disease, Therefore, it is critical to find green and sustainable drug treatment options. Natural drugs have wide sources, many targets, and high safety, and are currently recognized as ideal drugs for tumor treatment, has previously been found to have a good effect on controlling tumor progression and reducing the burden of metastasis. However, its clinical transformation is often hindered by structural stability, bioavailability, and bioactivity. Emerging technologies for the treatment of OC, such as photodynamic therapy, immunotherapy, targeted therapy, gene therapy, molecular therapy, and nanotherapy, are developing rapidly, particularly, nanotechnology can play a bridging role between different therapies, synergistically drive the complementary role of differentiated treatment schemes, and has a wide range of clinical application prospects. In this review, nanoscale natural drug delivery systems (NNDDS) for targeted drug delivery against OC were extensively explored. We reviewed the mechanism of action of natural drugs against OC, reviewed the morphological composition and delivery potential of drug nanocarriers based on the application of nanotechnology in the treatment of OC, and discussed the limitations of current NNDDS research. After elucidating these problems, it will provide a theoretical basis for future exploration of novel NNDDS for anti-OC therapy. [ABSTRACT FROM AUTHOR]

Background: Nanoparticle-mediated drug delivery aims to target specific cells, addressing the challenge that many drugs lack the necessary properties to reach their intended targets effectively. Lipid-based nanocarriers considered as a promising drug delivery due to their biocompatibility and ability to encapsulate various drugs. Surface modifications, including the attachment of polyethylene glycol for stability and the conjugation of targeting ligands (e.g., antibodies, peptides) for specific delivery, play a crucial role in enhancing the interaction of these nanocarriers with biological environments. These modifications improve cellular uptake and targeted delivery, thereby increasing therapeutic efficacy and reducing side effects. This review will explore various surface modification techniques and their impact on the performance of lipid nanocarriers in drug delivery. Main body: Lipid-based nanodelivery platforms have garnered significant interest due to their notable characteristics, including their ability to accommodate high drug loads, reduced toxicity, improved bioavailability, and compatibility with biological systems, stability within the gastrointestinal environment, controlled release capabilities, streamlined scaling up processes, and simplified validation procedures. Targeted lipid-based nanocarriers represent a significant advancement over non-targeted counterparts in cancer therapy. Unlike non-targeted systems, which distribute drugs indiscriminately throughout the body, targeted lipid-based nanocarriers can be engineered with ligands or antibodies to specifically recognize and bind to tumor-associated markers, enabling precise drug delivery to cancer cells. This targeted approach enhances therapeutic efficacy while minimizing adverse effects on healthy tissues, thereby offering a promising strategy for improving the outcomes of cancer treatment. Conclusion: The authors in this review provide an overview of preclinical research on diverse lipid-based nanocarriers, such as liposomes, solid lipid nanocarriers, and lipid polymer hybrid nanoparticles. The customization of these carriers using various surface modifiers is discussed, including folic Acid, peptides, polysaccharides, transferrin, and antibodies. Surface-modified nanocarriers offer regulated discharge, improved penetration capability, and precise drug conveyance. This work compiles recent instances of emerging surface-modified lipid-based nanocarrier systems and their applications, sourced from existing literature. Novel approaches to surface engineering of these nanocarriers, aimed at enhancing their specificity and efficacy in targeted drug delivery, were discussed. Key advancements in this field, such as improved targeting mechanisms and significant therapeutic outcomes demonstrated in preclinical studies, were highlighted. Additionally, critical gaps that require attention include long-term stability, biocompatibility, scalable production methods, regulatory challenges, and the necessary steps to transition from bench to bedside. [ABSTRACT FROM AUTHOR]

Background: The potential applications of nanotechnology in the medical field have become increasingly recognized in recent years. Nanocarriers have emerged as a versatile tool, offering a wide range of applications due to their unique properties. In addition to the targeted drugs delivery, nanocarriers have also proven to be extremely effective in imaging and diagnostics. Continuous advances in nanotechnology have paved the way for innovative solutions to complex challenges in human health, shaping the future of nanotechnology and its applications. Summary: By exploring different types of nanoparticles, this review delves into the different characteristics that can be tailored to enhance their kidney access. Although the structural complexity of the kidney may prevent nanocarriers passage, optimization of nanocarrier characteristics such as shape, size, charge, and surface modifications may overcome these barriers, allowing for targeted delivery. By harnessing the potential of nanoparticles, researchers aim to develop targeted and efficient therapies that can address various kidney-related disorders. Key Messages: This review highlights the promising advancements in nanotechnology and their potential impact on improving the therapeutic outcomes for several kidney diseases. [ABSTRACT FROM AUTHOR]

Designing and developing small organic molecules for use as urease inhibitors is challenging due to the need for ecosystem sustainability and the requirement to prevent health risks related to the human stomach and urinary tract. Moreover, imaging analysis is widely utilized for tracking infections in intracellular and in vivo systems, which requires drug molecules with emissive potential, specifically in the low-energy region. This study comprises the synthesis of a Schiff base ligand and its selected transition metals to evaluate their UV/fluorescence properties, inhibitory activity against urease, and molecular docking. Screening of the symmetrical cage-like ligand and its metal complexes with various eco-friendly transition metals revealed significant urease inhibition potential. The IC50 value of the ligand for urease inhibition was 21.80 ± 1.88 µM, comparable to that of thiourea. Notably, upon coordination with transition metals, the ligand–nickel and ligand–copper complexes exhibited even greater potency than the reference compound, with IC50 values of 11.8 ± 1.14 and 9.31 ± 1.31 µM, respectively. The ligand–cobalt complex exhibited an enzyme inhibitory potential comparable with thiourea, while the zinc and iron complexes demonstrated the least activity, which might be due to weaker interactions with the investigated protein. Meanwhile, all the metal complexes demonstrated a pronounced optical response, which could be utilized for fluorescence-guided targeted drug delivery applications in the future. Molecular docking analysis and IC50 values from in vitro urease inhibition screening showed a trend of increasing activity from compounds 7d to 7c to 7b. Enzyme kinetics studies using the Lineweaver–Burk plot indicated mixed-type inhibition against 7c and non-competitive inhibition against 7d. [ABSTRACT FROM AUTHOR]

Biological variability poses significant challenges in the development of effective therapeutics, particularly when it comes to drug solubility and bioavailability. Poor solubility across varying physiological conditions often leads to reduced absorption and inconsistent therapeutic outcomes. This review examines how nanotechnology, especially through the use of nanomaterials and magnetic nanoparticles, offers innovative solutions to enhance drug solubility and bioavailability. This comprehensive review focuses on recent advancements and approaches in nanotechnology. We highlight both the successes and remaining challenges in this field, emphasizing the role of continued innovation. Future research should prioritize developing universal therapeutic solutions, conducting interdisciplinary research, and leveraging personalized nanomedicine to address biological variability. [ABSTRACT FROM AUTHOR]

Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people's lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional 'natural' nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy. [ABSTRACT FROM AUTHOR]

Smart electrospun hybrid nanofibers represent a cutting‐edge class of functional nanostructured materials with unique collective properties. This review aims to provide a comprehensive overview of the applications of smart electrospun hybrid nanofibers in the fields of energy, catalysis, and biomedicine. Electrospinning is a powerful tool to fabricate different types of nanofibers’ morphologies with precise control over structure and compositions. Through the incorporation of various functional components, such as nanoparticles, nanomoieties, and biomolecules, into the (co)polymer matrix, nanofibers can be tailored into smart hybrid materials exhibiting responsiveness to external stimuli such as temperature, pH, or light among others. Herein recent advancements in fabrication strategies for electrospun smart hybrid nanofibers are discussed, focusing on different electrospinning tools aimed at tailoring and developing smart hybrid nanofibers. These strategies include surface functionalization, doping, and templating, which enable fine‐tuning of mechanical strength, conductivity, and biocompatibility. The review explores the challenges and recent progress in the development of smart hybrid nanofibers. Issues such as scalability, reproducibility, biocompatibility, and environmental sustainability are identified as key for improvement. Furthermore, the applications of smart nanofibers in biomedicine, environment, energy storage, and smart textiles underscore their potential to address the challenges in development of nanostructured materials for emerging technologies. [ABSTRACT FROM AUTHOR]

Isoniazid (INH) is amongst the first-line antibiotics that have been employed for the treatment of Tuberculosis (TB). Despite its potent anti-tubercular action, susceptibility to rapid hepatic first-pass metabolism and elimination largely limits its oral bioavailability, and has been associated with the induction of drug resistance and adverse effects. This presents study aims at the development and evaluation of unique mannosylated INH loaded solid lipid nanoparticles (Mn-INH-SLNs) for the treatment of TB. The Mn-INH-SLNs demonstrated a particle size of 466 ± 11 nm, which was acceptable for macrophage targeting and had % entrapment efficiency of 80.41 ± 1.37% (n = 6). The dissolution studies depicted a dual-phase drug release profile, i.e., burst release followed by a sustained release, revealing the best fit with the Korsmeyer-Peppas model. The MTT assay (cytotoxicity study) performed utilizing J774A.1 cells with optimized Mn-INH-SLNs deemed them to be safe and nontoxic. Mannosylated SLNs tagged with coumarin-6 (C6 – an established fluorescent marker) showed a substantially high intracellular internalization (1.11-folds) when analyzed through flow cytometric analysis (FACS). The in vivo pharmacokinetic evaluation following per-oral administration in rats demonstrated a significant rise in relative bioavailability (∼5.5-folds) with Mn-INH-SLNs compared to pure drug solution. The bio-distribution (drug disposition) studies exhibited greater lung accumulation of Mn-INH-SLNs (2.13-folds) in comparison to the unconjugated INH-SLNs (Un-INH-SLNs). The promising results of the study depict that the targeted-optimized Mn-INH-SLNs may be a propitious and potent tool to fight TB. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) are pivotal in maintaining vascular health, regulating hemodynamics, and modulating inflammatory responses. Nanocarriers hold transformative potential for precise drug delivery within the vascular system, particularly targeting ECs for therapeutic purposes. However, the complex interactions between vascular ECs and nanocarriers present significant challenges for the development and clinical translation of nanotherapeutics. This review assesses recent advancements and key strategies in employing nanocarriers for drug delivery to vascular ECs. It suggested that through precise physicochemical design and surface modifications, nanocarriers can enhance targeting specificity and improve drug internalization efficiency in ECs. Additionally, we elaborated on the applications of nanocarriers specifically designed for targeting ECs in the treatment of cardiovascular diseases, cancer metastasis, and inflammatory disorders. Despite these advancements, safety concerns, the complexity of in vivo processes, and the challenge of achieving subcellular drug delivery remain significant obstacles to the effective targeting of ECs with nanocarriers. A comprehensive understanding of endothelial cell biology and its interaction with nanocarriers is crucial for realizing the full potential of targeted drug delivery systems. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) manifests as inflammation in the colon, rectum, and ileum, presenting a global health concern with increasing prevalence. Therefore, effective anti-inflammatory therapy stands as a promising strategy for the prevention and management of IBD. However, conventional nano drug delivery systems (NDDSs) for IBD face many challenges in targeting the intestine, such as physiological and pathological barriers, genetic variants, disease severity, and nutritional status, which often result in nonspecific tissue distribution and uncontrolled drug release. To address these limitations, stimulus-responsive NDDSs have received considerable attention in recent years due to their advantages in providing controlled release and enhanced targeting. This review provides an overview of the pathophysiological mechanisms underlying IBD and summarizes recent advancements in microenvironmental stimulus-responsive nanocarriers for IBD therapy. These carriers utilize physicochemical stimuli such as pH, reactive oxygen species, enzymes, and redox substances to deliver drugs for IBD treatment. Additionally, pivotal challenges in the future development and clinical translation of stimulus-responsive NDDSs are emphasized. By offering insights into the development and optimization of stimulus-responsive drug delivery nanoplatforms, this review aims to facilitate their application in treating IBD. This review highlights recent advancements in stimulus-responsive nano drug delivery systems (NDDSs) for the treatment of inflammatory bowel disease (IBD). These innovative nanoplatforms respond to specific environmental triggers, such as pH reactive oxygen species, enzymes, and redox substances, to release drugs directly at the inflammation site. By summarizing the latest research, our work underscores the potential of these technologies to improve drug targeting and efficacy, offering new directions for IBD therapy. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective treatments for IBD and other chronic inflammatory diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

AbstractDecade-long efforts in medicinal biotechnology have enabled large-scale in-vitro production of optimised therapeutic RNA constructs for stable in-vivo delivery and modify the expression of disease-related genes. The success of lipid nanoparticle-formulated mRNA vaccines against Severe acute respiratory syndrome Coronavirus-2 (SARS-Cov2) has opened a new era of RNA therapeutics and non-viral drug delivery systems. The major limiting factor in the clinical translation of RNA-based drugs is the availability of suitable delivery vehicles that can protect RNA payloads from degradation, offer controlled release, and pose minimal inherent toxicity. Unwanted immune response, payload size constraints, genome integration, and non-specific tissue targeting limit the application of conventional viral drug-delivery vehicles. This review summarises current research on nano-sized drug carriers, including lipid nanoparticles, polymer-based formulations, cationic nanoemulsion, and cell-penetrating peptides, for targeted therapeutic RNA delivery. Further, this paper highlights the biomimetic approaches (i.e. mimicking naturally occurring bio-compositions, molecular designs, and systems), including virus-like particles (VLPs), exosomes, and selective endogenous eNcapsidation (SEND) technology being explored as safer and more efficient alternatives. [ABSTRACT FROM AUTHOR]

The blood‐brain barrier (BBB) poses a significant challenge in delivering therapeutic agents for brain diseases due to its high selectivity against foreign substances. This limitation greatly hampers the effectiveness of conventional chemotherapeutic drugs in treating brain cancers. In response, lipid‐based nanoparticles (LNPs) have emerged as a promising approach, offering opportunities for targeted drug delivery by conjugating targeting ligands onto their surface. This review provides a comprehensive overview of recent advancements in utilizing LNPs to traverse the BBB for enhanced transport of bioactive compounds into the brain, specifically for cancer treatments. Beginning with an exploration of the biological structure and functions of the BBB and the blood‐brain tumor barrier (BBTB), the review highlights the advantages presented by LNPs. Subsequently, it delves into strategies for surface modification of nanoparticles to enhance BBB targeting and improve efficacy in brain cancer treatment. Finally, the review offers insights into future prospects for designing the next generation of LNPs. The review presented herein aims to contribute to the ongoing efforts in overcoming the challenges associated with BBB penetration, ultimately advancing therapeutic strategies for brain cancer and other neurological disorders. [ABSTRACT FROM AUTHOR]

Functional nanocomposite materials are hybrid systems combining nanoscale fillers with a matrix, resulting in enhanced properties such as mechanical strength, thermal stability, and electrical conductivity. These materials are highly versatile, finding applications across a broad range of fields, including aerospace for lightweight, strong components, electronics for flexible and high-performance devices, healthcare for targeted drug delivery and tissue engineering, and environmental sectors for water purification and pollutant sensing. Their tunable properties make them ideal for addressing emerging challenges in various industries. This special issue entitled as "Functional Nanocomposite Materials" of Journal of Materials Science is a remarkable collection of invited and contributed papers on this topic, showcasing outstanding recent research results in this field. [ABSTRACT FROM AUTHOR]

Nanotechnology and nanorobotics have the potential to greatly enhance precision and therapeutic potential in neurosurgery. Traditional stereotactic neurosurgery uses a 3D coordinate system and imaging to target specific brain locations, but there is a risk of damaging healthy tissue. Nanorobots can autonomously or under control perform tasks such as drug delivery through the blood-brain barrier and reaching deep-seated areas of the brain. They can also be equipped with biosensors to detect specific biochemical markers and provide real-time data for diagnostics. However, there are challenges to address, including biocompatibility, precise control, regulatory frameworks, and accessibility. Close collaboration between engineers, neuroscientists, medical professionals, and regulatory bodies is necessary for successful integration of nanorobotics into neurosurgery. [Extracted from the article]

Motivation The prediction of drug–target interaction is a vital task in the biomedical field, aiding in the discovery of potential molecular targets of drugs and the development of targeted therapy methods with higher efficacy and fewer side effects. Although there are various methods for drug–target interaction (DTI) prediction based on heterogeneous information networks, these methods face challenges in capturing the fundamental interaction between drugs and targets and ensuring the interpretability of the model. Moreover, they need to construct meta-paths artificially or a lot of feature engineering (prior knowledge), and graph generation can fuse information more flexibly without meta-path selection. Results We propose a causal enhanced method for drug–target interaction (CE-DTI) prediction that integrates graph generation and multi-source information fusion. First, we represent drugs and targets by modeling the fusion of their multi-source information through automatic graph generation. Once drugs and targets are combined, a network of drug–target pairs is constructed, transforming the prediction of drug–target interactions into a node classification problem. Specifically, the influence of surrounding nodes on the central node is separated into two groups: causal and non-causal variable nodes. Causal variable nodes significantly impact the central node's classification, while non-causal variable nodes do not. Causal invariance is then used to enhance the contrastive learning of the drug–target pairs network. Our method demonstrates excellent performance compared with other competitive benchmark methods across multiple datasets. At the same time, the experimental results also show that the causal enhancement strategy can explore the potential causal effects between DTPs, and discover new potential targets. Additionally, case studies demonstrate that this method can identify potential drug targets. Availability and implementation The source code of AdaDR is available at: https://github.com/catly/CE-DTI. [ABSTRACT FROM AUTHOR]