International Journal of Nanomedicine最新文献

Purpose: This study aimed to investigate the mechanisms by which Astragalus polysaccharide nanoparticles (APS-CS/TPP) protect against septic myocardial injury, addressing the limited understanding of how APS-CS/TPP specific signaling pathways in this condition.

Materials and methods: Potential targets and pathways of Astragalus polysaccharide (APS) were initially predicted using network pharmacology, molecular docking, and microscale thermophoresis. APS-CS/TPP were prepared using an ion gel method with a chitosan derivative and characterized for formation, size, and surface charge. A murine model of septic myocardial injury was established by cecal ligation and puncture (CLP), and therapeutic outcomes were assessed via echocardiography, ELISA, histology, and Western blot. In vitro, H9c2 cells were stimulated with LPS and treated with APS-CS/TPP, with or without the HSP90AA1 inhibitor TAS-116, followed by evaluation of inflammatory markers and protein expression.

Results: APS showed high binding affinity to HSP90AA1. APS-CS/TPP improved survival and attenuated myocardial damage in septic mice. In vitro, they reduced levels of IL-1β, IL-6, and TNF-α, and downregulated HSP90AA1, NLRP3, caspase-1, and IL-1β. These effects were suppressed by TAS-116.

Conclusion: APS-CS/TPP protect against septic myocardial injury by inhibiting the HSP90AA1/NLRP3 signaling pathway.

Introduction: Magnetic Particle Imaging (MPI) is a radiation-free imaging modality based on the nonlinear magnetic response of iron oxide nanoparticles, providing high sensitivity and real-time, quantitative, background-free imaging. With the clinical approval of Resotran as an MPI-suitable tracer and the development of first human-scale scanners, clinical applications are within reach. Magnetic Particle Spectroscopy (MPS), the non-imaging counterpart of MPI, enables sensitive analytics by exploiting the signal response of magnetic nanoparticles. In this pilot study, we prove the potential of MPS to continuously monitor blood coagulation in real time.

Methods: Blood samples from five volunteers were mixed with the commercial magnetic resonance imaging contrast agent Resotran. The dynamics of the particle signal were assessed in a custom-built MPS-system for a duration of 45 minutes under various conditions, including the presence of anticoagulants (EDTA, Heparin, Citrate) and mechanical stress. The signal amplitude of the fifth harmonic of the MPS was analyzed. To exclude potential thermal effects, the temperature inside the MPS was monitored by using a fiber optic thermometer during the measurements.

Results: All Resotran-containing blood samples showed a signal decrease over time. Samples with anticoagulants exhibited no relevant signal decrease (EDTA, Citrate) or a smaller decrease (Heparin) compared to samples without anticoagulants. Additionally, mechanical stress induced a signal decay in all samples, further indicating the link between the observed MPS signal decay and blood coagulation.

Conclusion: This study shows that continuous monitoring of human blood coagulation via MPS is feasible, making bedside coagulation monitoring in clinical settings a concrete perspective.

Spinal cord injury (SCI) is a devastating condition associated with high rates of disability and mortality, as well as a significant financial burden. The current clinical interventions have limited therapeutic effectiveness, primarily due to relentless secondary injury cascades and the inherent challenge of neuronal circuit regeneration. Advances in biomaterials and fabrication technologies have led to the emergence of various novel formulations designed to specifically address these challenges and serve as a high-tech arsenal for researchers. This review delineates the pathophysiological mechanisms underlying SCI and the development of its self-propagating injury cascade. It also provides a comprehensive summary of recent advancements in the development and application of novel drug formulations, highlighting their distinct advantages in interrupting the injury cascade. This review aims to foster the development of more effective therapeutic strategies and ultimately improve therapeutic outcomes for patients with SCI.

Exosomes are membrane-bound vesicles secreted by almost all types of cells, including but not limited to immune cells, neurons, epithelial cells, and cancer cells. Exosomes carry DNA, RNA, lipids, metabolites, as well as cytoplasmic and cell surface proteins. Their role in cancer progression is dynamic and is related to the type of cancer, genetics, and stage. At the same time, exosomes have attracted widespread attention as key mediators of intercellular communication in the tumor immune microenvironment (TME). This comprehensive review delineates the pleiotropic roles of exosomes in tumor immunobiology, emphasizing their bimodal capacity to either foster immunosuppression or potentiate antitumor immunity. We systematically synthesize recent advancements in exosome-based immunotherapeutic regimens, with particular emphasis on their synergistic efficacy when integrated with established modalities, namely immune checkpoint blockade and adoptive cellular therapy. Furthermore, we critically appraise emergent technologies for exosome isolation and characterization, underscoring their transformative implications for liquid biopsy platforms in real-time immune surveillance and the development of predictive biomarkers. This review posits exosome-centric strategies as a paradigm-shifting frontier in precision immuno-oncology, furnishing innovative remedies for recalcitrant therapeutic hurdles and propelling the advancement of personalized oncology care.

Cancer remains a prominent cause of global mortality, with over 200 identified forms, and is projected to have a 25% increase in fatalities by 2030. Early diagnosis and treatment are crucial, but current therapy, which includes surgery, chemotherapy, immunotherapy, hormonal therapy, targeted therapy, and radiotherapy, faces challenges such as non-targeted drug distribution, toxicity, and limited efficacy. In recent years, biomimetic nanoparticles have emerged as a promising nanocarrier with great potential that enables site-specific drug release, improves biocompatibility, prolongs circulation time, and minimizes immune responses. Among various biomimetic nanoparticles, nanoparticles coated with cell membranes, such as those from cancer cells, immune cells, and stem cells, have been shown to have great potential for cancer treatment. The cell membrane-coated nanoparticles, further functionalized with tumor-specific ligands, demonstrated potential in improving half-life, drug specificity, and overall therapeutic efficacy. In this comprehensive article, we have reviewed recent advances in cell membrane-coated biomimetic nanoparticle systems for cancer therapy. We discussed the biomimetic nanoparticles coated with membranes of red blood cells, cancer cells, platelet cells, macrophages, exosomes, hybrid cells, and protein/serum albumin for cancer therapy. This review also highlights challenges associated with large-scale production, maintaining structural integrity during drug loading, clinical and biosafety aspects, regulatory requirements, and the clinical translation of the cell membrane-coated biomimetic nanoparticle systems.

The increasing global crisis of antibiotic resistance underscores the imperative for innovative antibacterial strategies that transcend conventional mechanisms. Ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, is a promising therapeutic approach. This review systematically explores ferroptosis-like death as an emerging antibacterial paradigm. The core mechanism involves exogenous interventions that result in intracellular iron overload, the incorporation of polyunsaturated fatty acids (PUFAs), and the disruption of bacterial antioxidant defenses. A comprehensive evaluation of three key strategies is provided: host-directed approach, in which immune cells are programmed to eliminate intracellular pathogens; small molecule-induced pathway, in which iron agents, PUFAs, and others are used to directly trigger bacterial death; and nanomaterial-mediated precision therapy, in which functionalized nanosystems are employed for synergistic and intelligent targeting. Despite the challenges in mechanistic understanding and biosafety, future advancements through multiomics, intelligent nanosystems, and synergistic cell death pathways are anticipated to propel this field. This strategy indicates a possible transformation in anti-infective therapy from broad-spectrum killing to precision regulation. This shift offers a potentially effective solution to address drug-resistant bacterial infections.

Gene therapy has great prospects of DNA/RNA manipulations and protein modulations. Its use in clinic is, however, stifled by risks of immunogenicity, low target specificity, and adverse effects. The red blood cell (RBC-EVs) extracellular vesicles can serve as a solution to this issue since they are biocompatible, long-term stable, and with low immunogenicity. RBC-EVs permit the accurate delivery of therapeutic cargo to space and time, thus minimizing systemic toxicity. This review presents the most recent developments on the expansion of the use of RBC-EVs to encapsulate the components of mRNA and CRISPR-Cas. Through the addition of the means to address these deficiencies, including stimulus-sensitive release mechanisms (eg, pH- or light-activated systems) and tissue-selective targeting approaches, RBC-EVs can be applied to enable the precise application in genetic diseases, inflammatory diseases, and cancer. Such innovations have the potential to overcome the clinical need and enable the biological complexity of mRNA- and CRISPR-Cas-based agents to provide a powerful delivery platform. Moreover, the review also demonstrates the unprecedented benefits of red blood cell EVs, which include immune evasion, scalability, and universal loading capacity, which can establish them as the next-generation delivery vehicles. Red blood cell EVs have the potential to increase the efficacy of precision medicine by increasing its feasibility. Lastly, we note the potential and translational issues in the provision of red blood cell EV-based mRNA and CRISPR-Cas therapeutic delivery of gene therapy.

Huntington's disease is a progressive neurological disorder marked by motor, cognitive, and psychiatric symptoms. Currently, there are no definitive diagnostic tools or effective treatments to halt or reverse the disease. In recent years, surface-engineered nanosystems have emerged as innovative therapeutic platforms, offering significant promise in overcoming the limitations of traditional approaches. These nano systems, including liposomes, dendrimers, polymeric nanoparticles, and solid lipid nanoparticles, offer significant potential by targeting and modulating intricate biochemical pathways involved in the progression of Huntington's disease. Their defining advantage lies in the ability to selectively deliver therapeutic agents to specific regions of the brain with high precision. Through the use of various nanoscale carriers, these particles can successfully traverse the protective barrier between the blood and brain tissue, enabling the direct delivery of treatment agents to the regions affected by Huntington's disease. This targeted approach not only enhances the therapeutic efficacy but also minimizes unwanted systemic side effects. This review highlights recent advancements in nanosystem development, addressing previous challenges and setbacks in the field, particularly in overcoming the blood-brain barrier and improving treatment delivery. The review further explores the evolving mechanisms of nanosystem delivery and their functional impact in experimental models of Huntington's disease. While the primary focus remains on therapeutic applications, we also briefly discuss recent developments in nanoparticle-based diagnostics. Although several challenges, particularly regarding comprehensive safety assessments and the current absence of nanoparticles approved by the United States Food and Drug Administration for Huntington's disease, this review underscores the transformative potential of nanosystems for future therapeutic applications.

Organ transplantation represents a definitive therapeutic modality for end-stage organ failure, yet it is plagued by formidable challenges encompassing allogeneic immune rejection and the inherent limitations of conventional immunosuppressive regimens. Nonspecific immunosuppression not only precipitates severe adverse events such as opportunistic infections and malignancies but also fails to precisely modulate the local immune microenvironment. The core innovation of this review lies in the systematic integration of the distinctive advantages of nanotechnology-including targeted delivery, multifunctional synergy, and stimuli-responsive intelligence-with transplant immune regulation, encompassing a comprehensive analysis spanning mechanistic elucidation, strategic optimization, and clinical translation. We first delineate the pivotal mechanisms underlying immune rejection, including the regulatory roles of the transplant immune microenvironment, T lymphocytes, macrophages, and oxidative stress in ischemia-reperfusion injury (IRI). Subsequently, we conduct a critical comparison between conventional immunosuppressants and emerging therapeutic strategies, with a particular focus on how nanoplatforms enable spatiotemporally precise immune modulation. This includes targeting the transplant immune microenvironment, reprogramming T cell/macrophage functions, mitigating oxidative stress, facilitating tissue repair and regeneration, as well as inducing immune tolerance via both active and passive approaches. Additionally, we discuss innovative nanotechnological strategies such as the optimization of organ cryopreservation protocols. In summary, nanotechnology offers a targeted, multifunctional, and long-acting paradigm for transplant immune regulation, albeit confronted with formidable translational bottlenecks. Future integration with interdisciplinary technologies will undoubtedly propel the field toward the goal of precision immune modulation in organ transplantation.

Background: Transdermal drug delivery is a local and non-invasive method for treating skin diseases that offers advantages such as sustained and long-term drug release.

Methods: In this study, transfersomes (TFs) containing human Insulin-like growth factor 1 (TF/hIGF-1) were prepared and characterized as an effective transdermal drug delivery system to improve skin wound healing in diabetic models. TFs were prepared using the film hydration method and characterized by various methods.

Results: Pre-release evaluation confirmed the controlled release of human insulin-like growth factor (hIGF-1) supported by TEM images, showing dispersed spherical shapes with particle sizes below 100 nm. In vitro studies of these nanovesicles demonstrated that encapsulation significantly improved the stability and functionality of hIGF-1, enhancing cell migration and complete closure of cell monolayer gaps. In vivo studies on diabetic rats treated with TF/hIGF-1 hydrogel revealed accelerated wound healing compared to controls. Histopathological analysis also showed increased epidermal thickness and dermal protrusions, indicating enhanced healing effects.

Conclusion: Overall, this study demonstrated that hIGF-1 released from TF/hIGF-1 in a controlled manner could effectively promote re-epithelialization and granulation tissue formation in diabetic wounds of animal models compared to controls. These findings suggest a promising and effective approach for potential use in treating diabetic wounds.