International Journal of Nanomedicine最新文献

The clinical management of bone defects presents a significant challenge in regenerative medicine due to the limited self-repair capacity of bone tissue and inadequate vascularization. Nitric oxide, a gaseous signaling molecule, has garnered attention as a potent modulator of bone remodeling, exhibiting pro-osteogenic, pro-angiogenic, and anti-inflammatory properties. However, its therapeutic application is limited by its short half-life, high reactivity, and dose-dependent biphasic effects. Advanced polymer-based nanoformulations have been developed to address these challenges and enable controlled and localized NO delivery to bone tissue. This review explores role of NO in bone repair mechanisms and the limitations of conventional delivery systems. Significant focus is given to innovative polymeric platforms, such as dendrimers, micelles, nanogels, and hybrid composites, which offer precise control over release kinetics, high encapsulation efficiency, and targeted delivery. Additionally, integrating NO delivery within nanoengineered scaffolds and coatings for orthopedic implants is explored as a promising strategy to enhance osteointegration and reduce the risk of post-surgical infections. Preclinical studies demonstrate promising osteogenic effects yet face significant challenges including cytotoxicity at elevated NO concentrations along with non-standardized evaluation protocols and scalability limitations. Future perspectives point to the potential of stimuli-responsive systems, co-delivery approaches, and personalized strategies utilizing additive manufacturing technologies. This review consolidates the latest advancements in the field, underscoring the significant potential of polymer-based NO nanoformulations to revolutionize bone tissue engineering.

Glioblastoma (GBM) is the most aggressive primary brain tumor, with median survival rates remaining dismally low despite standard-of-care therapies including maximal resection, radiation, and chemotherapy. A significant challenge in GBM therapy is the inability of conventional drugs to achieve therapeutic concentrations in the tumor due to the restrictive nature of the blood-brain barrier (BBB) and the complex tumor microenvironment (TME), which includes high interstitial pressure, abnormal vasculature, and dense extracellular matrix that together hinder drug penetration and distribution. Nanoparticle-based drug delivery systems have emerged as promising tools to circumvent the BBB and enhance drug delivery for GBM treatment. Among these, poly(lactic-co-glycolic acid) (PLGA) formulations stand out as one of the most widely used biodegradable carriers, which have been approved by the FDA for drug delivery applications. This review provides a comprehensive evaluation of the challenges and opportunities arising from the GBM microenvironment and their implications for the development of PLGA nanoparticle-based drug delivery systems. We compare commonly used PLGA nanoparticle synthesis techniques and analyze key GBM characteristics that impede drug transport, highlighting how tumor microenvironmental constraints govern nanoparticle engineering and delivery efficiency. We further evaluate the integration of multimodal therapies that affect both therapeutic delivery and outcomes. Critically, we identify persistent translational bottlenecks and outline specific research and engineering solutions to bridge preclinical efficacy and clinical translation. By integrating current evidence through a translational perspective, this review offers researchers and clinicians a strategic roadmap to guide future efforts toward more rational nanoparticle design and successful clinical translation for GBM therapy.

Among gynecologic malignancies, ovarian cancer (OC) stands out as a highly aggressive disease with the highest mortality rate and the poorest prognosis. At the beginning stage, it demonstrates high sensitivity to platinum-based chemotherapy. Nevertheless, most patients will encounter recurrence following the initial surgery and chemotherapy. Small extracellular vesicles (sEVs), characterized by a "cup-shaped" morphology and with a diameter of 40 to 160 nm, encompass diverse biologically active substances including nucleic acids (such as DNA, mRNA, microRNA (miRNA), and other non-coding RNAs (ncRNAs)), as well as oncogenic proteins, lipids, and metabolites, which play a crucial role as mediators of intercellular communication. Increasing evidence shows that sEVs promote various cancers' progression (including OC) via transporting molecular cargoes to target cells or organs. It is worth mentioning that existing literature often focuses on sEVs from a single cell type and lacks a comprehensive review of multiple cell sources. In this review, we summarize the biological functions of sEVs derived from different cell types in OC, including regulating cell proliferation, promoting metastasis, mediating drug resistance, inducing angiogenesis, facilitating immune escape, and maintaining stemness. Meanwhile, we focus on exploring the clinical value of sEVs as biomarkers for the diagnosis and prognosis of OC, as well as their application potential in translational medicine fields related to cancer vaccine development, targeted drug delivery, and precision tumor-targeted therapy. Additionally, we analyze the major challenges currently faced in sEV-based OC treatment research and propose potential strategies to overcome these limitations.

As global population aging intensifies, the incidence of central nervous system (CNS) disorders escalates, while obstacles like the blood-brain barrier (BBB) impede effective medication delivery. Plant-derived exosome-like nanovesicles (PELNVs), as innovative therapeutic carrier, have garnered significant interest in their capacity to transport medications across the BBB. A substantial emphasis is focused on the diverse therapeutic potential of PELNVs, underscoring their direct neuroprotective, anti-inflammatory, and antioxidant properties, along with their nascent function in altering the gut-brain axis to indirectly mitigate neuroinflammation. We subsequently compile information elucidating the processes by which PELNVs transport therapeutic cargo to the brain, including receptor-mediated transcytosis and their tailored targeting techniques. Ultimately, we address the prevailing difficulties. In summary, PELNVs embody a revolutionary, multi-faceted strategy with significant promise to address the persistent challenges in CNS medication delivery and treatment.

Purpose: To develop everolimus-loaded nanosuspensions (EV-sus) for the in vitro and in vivo corneal neovascularization (CNV) treatment.

Results: Everolimus was encapsulated into nanosuspensions using a solvent volatilization technique. The developed nanosuspensions exhibited a drug concentration of 0.96 mg·mL^-1, an average particle size of 141.0 ± 1.0 nm, and a zeta potential of -12.2 ± 0.4 mV. C6-labeled EV-sus uptake by Human Corneal Epithelial Cells-Transformed (HCE-T) was time-dependent, energy-dependent, and involved multiple endocytic pathways, including caveolae- and lipid raft-mediated endocytosis, clathrin-mediated endocytosis, and caveolae-mediated endocytosis. The nanosuspensions exhibited efficacy in inhibiting VEGF-induced proliferation, migration, and tube formation in Human Umbilical Vein Endothelial Cells (HUVECs). According to RT-qPCR, the in vivo CNV model showed that EV-sus effectively reduced neovascularization, decreased vascular length and area, and diminished the expression of IL-1, IL-6, MMP-9, VEGF, and TNF-α. Additionally, the rabbit eye irritation test confirmed the safety and tolerability of the formulation.

Conclusion: These findings indicate that EV-sus might be an effective therapy for corneal neovascularization. The formulation exhibits excellent biocompatibility, efficient cellular uptake, and robust anti-angiogenic activity, suggesting its suitability for ocular administration and the potential to mitigate CNV progression with minimal irritation.

Metal ions exert indispensable functions in various physiological processes, and metal ion homeostasis is needed in cells. Intracellular metal ion homeostasis is regulated by their efflux and influx across the cell membrane. Dysregulation of intracellular metallic ions can trigger programmed cell death (PCD). In recent years, metallic ions as potent immunomodulators and enhancers for cancer immunotherapy through modulating the immunosuppressive tumor microenvironment and triggering an immunostimulatory response have been extensively explored. The review focuses on the mechanism of PCD and immunomodulatory effects for various metal ions including iron, copper, calcium, zinc, and manganese, and provides a systematic overview of nanoparticles for delivering metallic ions or constructed of metals to realize PCD and enhance cancer immunotherapy. Finally, the prospect and challenges of clinic translation of metal-based nano-drug delivery systems in cancer therapy are outlined, and especially restriction of large-scale manufacturing and safety concern for clinic translation are further discussed.

Selenium nanomaterials, as current emerging materials, have garnered significant attention in the medical field due to their remarkable bio-compatibility, low toxicity, and environmental sustainability. Due to their facile synthetic accessibility and tunable physicochemical properties, they exhibit significant potential as novel adjuvant therapeutic strategies for treating inflammation, bacterial infections, and other pathological conditions. This review first systematically outlines three primary synthesis strategies for Selenium nanoparticles(SeNPs): physical, chemical, and biological approaches, highlighting their respective underlying mechanisms and unique advantages. Then it summarizes the properties of various SeNPs and the advantages and disadvantages of each method, assessing and providing a comprehensive comparison of the strengths and limitations associated with each synthesis method. Furthermore, this review introduces the molecular mechanisms underlying the anti-inflammatory, antioxidant, and antimicrobial activities of SeNPs, with a focus on the signaling pathways and enzymatic interactions through which SeNPs exert their therapeutic effects in vivo. Finally, this review summarizes recent advancements in the application of SeNPs in three critical areas: antimicrobial therapy, cancer treatment, and anti-inflammatory/antioxidant interventions, focusing on summarizing the current application of SeNPs and exploring the possibility of their application in the field of stomatology by elucidating their strengths and weaknesses, which provides a theoretical basis for SeNPs' application in the field of stomatology.

Introduction: Metal oxide nanoparticle-loaded hydrogel beads have recently emerged as a promising tool for controlled release applications. This study explores the synthesis and characterization of amine-functionalized nickel cobalt ferrite (NiCoFe₂O₄) nanoparticles (ANiCoFe NPs) embedded within sodium alginate/polyvinyl alcohol (SAPVA) hydrogel beads for the controlled release of 5-fluorouracil (5-FU).

Methods: ANiCoFe NPs were synthesized via chemical co-precipitation, and the NP-loaded hydrogel beads were prepared using ionotropic gelation. The hydrogel beads were characterized by various techniques including FTIR, XRD and TGA. In vitro release studies were performed at pH 7.4 and 2.0 at 37°C, and cytotoxicity was evaluated on MCF-7 and MCF-10 cells.

Results: Scanning electron microscopy revealed a highly porous hydrogel structure. Thermal and degradation analyses demonstrated that NP incorporation enhanced hydrogel stability. Release studies confirmed pH-responsive behaviour. Cytotoxicity assays showed that 5-FU/NP-loaded beads significantly reduced MCF-7 cell viability, whereas SAPVA and NP-loaded beads without drug exhibited negligible toxicity toward MCF-10 cells.

Discussion: The developed hydrogel beads are pH-responsive and provide controlled drug release, with their ROS-generating capability enhancing their potential for therapeutic applications.

Purpose: The traditional construction of targeted ultrasound molecular imaging probes relies on multistep chemical synthesis strategies, which are time-consuming and inefficient, thereby limiting technological advancements. To address this, we developed a novel genetic engineering approach for biosynthesizing targeted nanoprobes for prostate cancer diagnosis.

Materials and methods: The anti-PSMA nanobody-encoding gene was fused to the C-terminus of the gas vesicle structural protein gene GvpC and cloned into a pBV220 plasmid with a hyperthermia-responsive gene expression circuit. This recombinant plasmid was transformed into E. coli BL21(A1) harboring pET-28a-ΔGvpC-eGVs plasmids to create PSMA-GVs@E. coli genetically engineered bacteria. The probe assembly were involved in two-step gene expression procedure. ΔGvpC-eGVs were first induced by IPTG, followed by temperature-triggered (42°C) production of PSMA-GvpC proteins that spontaneously assembled onto GVs.

Results: The biosynthesized PSMA-eGVs probes exhibited a uniform size (100-200 nm) and demonstrated excellent targeting capability in prostate cancer cells. In vivo studies confirmed effective tumor vascular penetration and specific binding with PSMA-positive tumor cells, resulting in significantly stronger acoustic signals than the non-targeted EGFP-eGVs controls.

Conclusion: This cellular synthesis strategy enables efficient production of targeted ultrasound molecular imaging probes through genetically engineering technology, providing a promising platform for precision cancer diagnostics.

Siderophores are low-molecular-weight iron chelators that mediate microbial iron acquisition and critically shape host-pathogen interactions. This review highlights the structural diversity, regulatory networks, and virulence functions of bacterial siderophores, including their roles in overcoming host nutritional immunity, modulating immune responses, promoting biofilms, and coordinating metal homeostasis. We further discuss therapeutic strategies that exploit siderophore pathways, from "Trojan horse" siderophore-antibiotic conjugates such as cefiderocol to emerging non-antibiotic conjugates incorporating metal complexes, peptides, nucleic acids, vaccines, and nanomaterials. Beyond antibacterial applications, siderophores show promise in antifungal and antiparasitic therapies and as infection-specific imaging probes. Despite these advances, translational challenges-including adaptive resistance, pharmacokinetic instability, and competition with endogenous siderophores-limit clinical progression. Innovative approaches such as engineered siderophore scaffolds, multifunctional delivery platforms, and nanotechnology-enabled systems may help overcome these barriers. Overall, this review underscores the central role of siderophores in microbial pathogenesis and their growing potential as versatile platforms for next-generation anti-infective and diagnostic development.