International Journal of Nanomedicine最新文献

This narrative review synthesizes the latest advances in nano-diagnostic and therapeutic reagents for acute pancreatitis (AP), based on peer-reviewed experimental and preclinical studies published in recent years. AP endangers life through self-digestion of pancreatic tissue and a cascading systemic inflammatory reaction. In clinical practice, the existing diagnostic and therapeutic tools are limited by low sensitivity and insufficient targeting, so it is difficult to achieve the ideal diagnosis and treatment effect of AP. However, the emerging nanotechnology is expected to overcome these drawbacks by offering highly specific delivery systems and ultrasensitive detection platforms. The studies included in this review are directly related to nanomedicine diagnosis, treatment, and diagnosis and treatment of AP, and are categorized by their functional implementation pathways to emphasize technological translational potential. For diagnosis, nano-sensors (optical, electrochemical) and contrast agents (MRI-responsive nanoparticles) enable early detection of biomarkers and precise imaging of pancreatic lesions. For treatment, nano-reagents address barriers like the blood-pancreatic barrier, low drug specificity, and insufficient intervention in the pathogenesis through multi-faceted strategies: targeted delivery systems, microenvironment-responsive release, and biological pathway regulation. Theranostic nano-reagents integrating diagnosis and therapy show promise for real-time monitoring and intervention. In the end, it emphasizes the need for further optimization of biocompatibility and clinical validation and provides insights for clinical strategy design.

Acute Lung Injury (ALI) and its severe manifestation, Acute Respiratory Distress Syndrome (ARDS), represent critical clinical challenges characterized by diffuse alveolar damage, uncontrolled inflammatory storms, and oxidative stress. Despite supportive therapies such as mechanical ventilation have advanced considerably, mortality rates remain persistently high. Over the past five years, Carbon Dots (CDs)-a novel class of zero-dimensional carbon nanomaterials-have demonstrated significant potential for the precision theranostics of ALI/ARDS due to their ultra-small size (<10 nm), tunable photoluminescence, superior biocompatibility, and intrinsic enzyme-mimicking activities. This review comprehensively synthesizes frontier advancements in CDs applications for pulmonary diseases over the past five years. We systematically elucidate eco-friendly synthesis strategies, surface functionalization (eg, mannose and RGD peptide targeting), and the mechanisms by which CDs function as nanozymes (mimicking SOD, CAT, and POD) to scavenge reactive oxygen species (ROS). Particular emphasis is placed on novel therapeutic strategies, including the modulation of the gut-lung axis to remodel intestinal flora and the construction of ROS-responsive smart drug delivery systems (eg, for siRNA and glucocorticoids). Furthermore, we compare the inhalation toxicology of CDs against traditional carbon materials like carbon nanotubes and evaluate their utility in in vivo lung inflammation imaging and microenvironmental sensing (NO, pH). This review aims to provide a theoretical foundation and strategic direction for the clinical translation of CD-based nanomedicine.

Sensorineural hearing loss (SNHL) is a prevalent global health issue, and its pharmacological treatment is severely hindered by the blood-labyrinth barrier (BLB). Exosomes, natural extracellular vesicles (30-150 nm), have emerged as a highly promising nanoplatform to overcome this delivery challenge. Their innate biocompatibility, low immunogenicity, and ability to cross biological barriers make them ideal for targeted drug delivery. This review examines the inner ear barrier systems and elucidates the mechanisms, such as receptor-mediated transcytosis, by which exosomes can traverse the BLB. It further discusses engineering strategies to optimize drug loading, enhance targeting, and improve therapeutic efficacy for SNHL. The application of engineered exosomes in delivering diverse cargoes-including nucleic acids, proteins, and small-molecule drugs-is comprehensively reviewed, highlighting their potential in preclinical models to preserve auditory function. Despite this promise, significant challenges remain in standardization, scalable production, loading efficiency, long-term safety, and clinical translation. Future research should focus on refining engineering techniques, elucidating in vivo pharmacokinetics, and advancing preclinical studies to facilitate the clinical adoption of exosome-based therapies, ultimately offering a novel and precise paradigm for SNHL treatment.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) poses a major challenge due to the lack of effective treatment options and its extremely poor prognosis. Nanodrug delivery systems can improve drug solubility and enable efficient targeted delivery, offering new possibilities for PDAC therapy.

Methods: The oncogenic role of KCa3.1 in PDAC was validated through analyses of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases combined with functional assays. To overcome the limitations of conventional therapies, we developed a targeted nanodrug delivery system, TRAM@PPF, based on PLGA nanoparticles modified with polyethylene glycol-folate (PEG₂₀₀₀-FA). This system was prepared by the emulsion-solvent evaporation method to specifically deliver the KCa3.1 channel inhibitor TRAM-34 to PDAC cells. We characterized the nanosystem's physical properties and release profile and evaluated its antitumor efficacy in vitro and in vivo.

Results: The synthesized TRAM@PPF nanoparticles demonstrated uniform size (~142 nm) and excellent stability, with superior cellular uptake compared to non-folate-modified nanoparticles. In vitro, TRAM@PPF showed potent antitumor activity by markedly inhibiting cell proliferation and enhancing apoptosis. Following intravenous administration in pancreatic cancer mouse models, TRAM@PPF significantly inhibited tumor growth, reduced tumor weight, and prolonged survival. Moreover, TRAM@PPF showed excellent biosafety in animal models, suggesting strong potential for further clinical translation in PDAC therapy.

Conclusion: TRAM@PPF preserves folate-mediated tumor-targeting capability while significantly enhancing antitumor activity, offering a promising strategy for targeted therapy of pancreatic cancer.

The process of wound healing is intricate and, once disrupted, results in scar formation. Scar formation has negative physiological and psychological impacts on patients in addition to impeding the restoration of skin integrity and function. Increasing evidence indicates that factors such as angiogenesis, ECM deposition, and inflammation are all associated with scar formation. Given their excellent immunomodulatory and regenerative properties, mesenchymal stem cell-derived exosomes (MSCs-Exos) are increasingly favored in inhibiting scar formation during wound healing. This review begins with a summary of the key mechanisms of wound healing and scar formation, followed by the application of MSCs-Exos in attenuating the pathological process of scar formation, as well as its potential mechanisms of action. In addition, the current status and development prospects of engineered exosomes and hydrogel-combined exosomes in scar inhibition are further discussed. Finally, we evaluate the current challenges of using exosomes for scarless wound healing, including manufacturing standardization, dosing, delivery systems, and the lack of large-scale clinical data, which hold the potential to bridge the gap between the laboratory and the clinical.

Purpose: Gadolinium-based contrast agents (GBCAs), which are indispensable for magnetic resonance imaging (MRI), carry a severe risk of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD), particularly in those with advanced renal impairment. This critical safety concern necessitates the development of biocompatible alternatives that do not compromise diagnostic efficacy.

Materials and methods: Inulin-based nanoparticles (Inulin@Gd/Zn NPs) were synthesized by chelating inulin with gadolinium and zinc ions, aimed at being used as contrast agents that can replace conventional GBCAs. The morphology, size, and zeta potential of the nanoparticles were determined. The anti-fibrotic ability of Inulin@Gadolinium/zinc nanoparticles (Inulin@Gd/Zn NPs) was evaluated in vitro and in vivo, as well as their MRI imaging ability and metabolic performance in normal and fibrotic kidneys. A unilateral ureteral obstruction (UUO) model was created in mice and was used to evaluate the in vivo anti-fibrotic efficacy.

Results: The ultra-small Inulin@Gd/Zn NPs (<10 nm) exhibited high stability and T1 relaxivity. Compared to Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), Inulin@Gd/Zn NPs demonstrated precise kidney targeting, excellent T1-weighted MRI capabilities, and rapid renal clearance. In vitro studies showed that Inulin@Gd/Zn NPs had very low cytotoxicity for HK-2 cells up to 100 µM. Further, the NPs were able to reduce reactive oxygen species generation in hydrogen peroxide-stimulated HK-2 cells. Negligible levels of hemolysis and organ toxicity were confirmed in vivo. Further, in the UUO model, administration of Inulin@Gd/Zn NPs was found to significantly inhibit fibrosis. Both in vitro and in vivo experiments demonstrated that Inulin@Gd/Zn alleviated GBCA-induced early tubulointerstitial fibrosis by inhibiting the transforming growth factor-β1 (TGF-β1) signaling pathway.

Conclusion: Inulin@Gd/Zn NPs represent a promising strategy for clinical application of GBCAs. It addresses the diagnostic and therapeutic challenges in patients with CKD, offering a paradigm shift in the safe application of GBCAs in high-risk populations, indicating the need for further clinical trials to enable clinical applications.

Kidney-targeted drug delivery is pivotal for treating renal diseases while minimizing systemic toxicity. To navigate the organ's complex physiological barriers, advanced nanomedicines employ integrated strategies. Our comprehensive narrative review provides a structured analysis of these strategies through a dual lens: first, by examining the fundamental mechanisms of renal targeting-including passive filtration, active receptor-mediated uptake, and their synergistic combination; and second, by deconstructing delivery systems into several fundamental pillars, the carrier platforms, the functional moieties that confer targeting, responsiveness and special properties along with therapeutic cargo. We evaluate how polymeric nanoparticles, liposomes, and exosomes, when functionalized with peptides, antibodies, or biomimetic coatings, can achieve enhanced renal specificity. Furthermore, we discuss how microenvironmental triggers such as pH, reactive oxygen species, and enzymes enable precise spatiotemporal drug release at pathological sites. Despite significant progress, critical translational challenges remain, including overcoming hepatic sequestration, ensuring long-term biocompatibility, and addressing patient heterogeneity. Future advances will depend on combining multimodal targeting, real-time feedback, and scalable manufacturing processes. This review synthesizes current knowledge to offer a rational design framework for the next generation of intelligent kidney-targeted therapeutics.

Vision impairment represents a significant and growing global socioeconomic burden. In the elderly population, cataracts, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are the predominant causes of visual loss. Conventional ophthalmic drug therapies are limited by low bioavailability and dose-related toxicity, highlighting the urgent need for safer and more effective treatments. Selenium (Se), an essential trace element, is critical for antioxidant defense, redox homeostasis, and immune regulation. Although the roles of elemental Se in ocular physiology and diseases are well-documented, its clinical application is constrained by its narrow therapeutic window and poor bioavailability. To overcome these limitations, Se nanoparticles (SeNPs) have emerged as a superior alternative, offering enhanced bioavailability, reduced toxicity, and the capability for targeted drug delivery. Strong preclinical evidence supports the therapeutic potential of Se nanomedicines in models of DR, retinal neovascularization, infectious keratitis, and cataracts. Significantly, the initial stages of clinical translation are in progress, as demonstrated by a pioneering Phase I trial involving CdSe/ZnS quantum dots (QDs) in patients with retinitis pigmentosa (RP), which has shown both tolerability and improvements in visual function. This review provides a comprehensive and up-to-date analysis of Se-based nanomedicines for ocular diseases, based on a literature search of PubMed, Scopus, Web of Science, and Google Scholar. It elucidates how SeNPs uniquely synergize intrinsic multi-mechanistic bioactivities (e.g., antioxidant, anti-angiogenic) with targeted and stimuli-responsive drug delivery, establishing them as versatile nanoplatforms with significant clinical translation potential for complex ocular pathologies. Therefore, further research is essential to optimize their design, elucidate their mechanisms of action, and ultimately facilitate their safe and effective clinical translation.

Cancer therapy has long been constrained by challenges such as high recurrence rates, high metastasis rates, and damage to normal tissues, and conventional therapeutic approaches struggle to achieve a precise balance between efficacy and safety. The innovation of nanotechnology has brought breakthroughs to this field. As a typical class of zero-dimensional carbon-based nanomaterials, carbon dots (CDs) generally exhibit a size of less than 10 nm. Owing to their favorable biocompatibility and abundant surface functional groups, CDs offer a novel avenue for tumor therapy. This review systematically summarizes the various application strategies, mechanisms of action, and research progress of CDs in cancer therapy. First, it introduces two critical functions of CDs in tumor therapy: drug delivery and targeting. Subsequently, we delve into the applications of CDs in a series of anticancer strategies, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), gas therapy (GT), immunotherapy, gene therapy, and nanozyme-based therapy. Finally, the challenges faced by CDs in cancer therapy are summarized, and their future development directions are prospected, providing theoretical references and research ideas for the clinical translation of CD-based tumor therapeutic systems.

Given the intricate anatomy of otolaryngology-head and neck (OHNS) regions and the inherent limitations of conventional therapies, many OHNS diseases have suboptimal clinical outcomes. As natural intercellular mediators, exosomes have demonstrated unique application potential in OHNS treatment in recent years, thanks to their high biocompatibility, low immunogenicity, and intrinsic targeting capabilities. However, such issues as limited drug-loading capacity, suboptimal in vivo stability, and insufficient targeting precision still hinder their clinical translation. Notably, recent advances in engineering strategies such as genetic editing, surface modification, and optimized drug loading enhance natural exosomes' functionality, boosting targeting accuracy, in vivo stability, and therapeutic efficacy. Considering conventional therapy limitations and engineered exosomes' unique potential, this review synthesizes their progress, mechanisms, and translational challenges in OHNS, and addresses lingering technical and translation barriers via interdisciplinary collaboration to optimize their design, utility, and bench-to-bedside translation, as these exosomes are promising precision tools for refractory OHNS diseases advancing precision medicine in the field.