International Journal of Nanomedicine最新文献

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, hampered by prolonged, toxic treatment regimens that lead to poor patient adherence and drug resistance, as well as diagnostic tools that lack sensitivity and specificity. This systematic review evaluates recent advancement in actively targeted nanoparticle (NP) systems designed to improve TB diagnosis, treatment, and vaccination. Peer-reviewed studies published after 2015 focusing on NPs with active targeting capabilities were analyzed. The findings show that: ligand-functionalized NPs achieve precise, receptor-mediated targeting of infected cells, enhancing therapeutic efficacy; integrating diagnostic elements into these platforms enables rapid, sensitive biomarker detection; and antigen-loaded NPs effectively modulate immune responses, showing significant promise for novel vaccine development. Therefore, actively targeted NPs represent a transformative platform to overcome critical limitations in TB care by offering a unified strategy to improve diagnostic accuracy, therapeutic outcomes, and vaccine-induced immunity.

The expanding protein-based drug market is facing limitations from invasive delivery methods. These methods can cause discomfort and pose infection risk, particularly for the chronic disease patients such as diabetes requiring insulin with adherence challenges. Oral insulin, though preferred, suffers from <2% bioavailability, thus, nano-drug delivery system (NDDS) is becoming a highly promising strategy to enhance bioavailability and stability. However, the low expression of receptors and limited uptake capacity remain challenge. The use of cell-penetrating peptides (CPPs) will enhance the permeability of epithelial cells, and combining them with nanoparticles (NPs) can further improve the stability of protein-based drugs in blood circulation and facilitate the development of efficient delivery carriers. This comprehensive review delves into the design, synthesis, classification, challenges, and cellular uptake mechanisms of CPPs-cargo complexes and CPPs-NP nanocarriers for insulin delivery. Furthermore, it provides an in-depth exploration of the challenges and prospects of these innovative approaches.

Exosomes are nanoscale extracellular vesicles secreted by various cell types and have become key mediators of intercellular communication, immune regulation, and tissue regeneration. With advancements in inhalable or nebulized formulations, their potential as therapeutic agents has been significantly enhanced, allowing for targeted delivery to the respiratory system while minimizing systemic side effects. This review provides a comprehensive overview of the fundamental biology, biogenesis, and cargo composition of exosomes, emphasizing their role in intercellular signaling and low immunogenicity. The rationale for local pulmonary delivery is discussed, highlighting advantages such as enhanced bioavailability, reduced systemic exposure, and improved patient compliance. Current preclinical and clinical studies demonstrate the efficacy of inhaled exosomes in treating acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and lung cancer. Additionally, exosomes exhibit promising immunomodulatory and anti-aging properties, including macrophage polarization, alleviation of cytokine storms, and mitochondrial restoration. Challenges surrounding large-scale production, standardization, and regulatory approval are addressed, while the prospects for engineering exosomes with enhanced payloads and specificity are envisioned. The combination of nanotechnology and biomimetic systems, along with personalized medicine approaches, underscores the transformative potential of inhaled exosomes in respiratory and systemic therapies.

Rheumatoid arthritis (RA) affects approximately 1% of the global population, causing debilitating joint pain and often leading to severe disability. Although conventional treatments can control the initial symptoms of RA, there is no curative treatment strategy for RA. Biomimetic nanomedicine has emerged as a promising therapeutic approach, leveraging the integration of nanoparticles with natural biomaterials to achieve targeted drug delivery and improved treatment outcomes. Beyond exogenous nano-delivery systems, the natural biomimetic strategy might offer superior biocompatibility and lower immunogenicity. This review summarizes the latest advancements in biomimetic drug delivery systems for RA and highlights the underlying mechanisms for these biomimetic carriers. We also discuss the critical factors influencing the transition of these biomimetic nanomedicines from laboratory research to clinical implementation. By emphasizing the transformative potential of biomimetic strategies in RA treatment, this review aims to provide new insights and directions for future research and clinical applications in this field.

Acute lung injury (ALI) remains a critical clinical challenge characterized by uncontrolled inflammation, oxidative stress, and immune dysregulation, with limited therapeutic options and high mortality. In recent years, biomimetic nanoplatforms-including those derived from cell membranes, extracellular vesicles (EVs), and hybrid biological interfaces-have emerged as transformative tools for ALI management. Unlike conventional nanocarriers, these systems reproduce natural intercellular communication and immune evasion mechanisms, thereby achieving precise lung targeting, sustained therapeutic delivery, and coordinated regulation of inflammation and tissue repair.This review provides a comprehensive and mechanistic overview of biomimetic nanoplatforms in ALI therapy, with an emphasis on membrane-derived, EV-based, and hybrid nanosystems. We further introduce less-explored biomimetic strategies, including protein-, bacterial-, and virus-inspired nanoparticles, to expand the conceptual framework of biological mimicry in pulmonary nanomedicine. Beyond summarizing progress, we critically discuss key translational barriers-immunogenicity, model fidelity, and large-scale manufacturing-and propose integrative solutions leveraging artificial intelligence, organ-on-chip technologies, and precision medicine approaches.By offering a unified perspective on the design, function, and translational roadmap of biomimetic nanotherapeutics, this review highlights how the integration of biology-inspired engineering and pulmonary pathophysiology could pave the way toward personalized and clinically viable nanomedicine for ALI.

Nanotherapeutics based on platelet membranes represent a new and advanced biomimetic approach in nanomedicine. By covering synthetic nanoparticle cores with natural platelet membranes, these platforms ingeniously combine the multifaceted biointerfacing abilities of platelets, such as long circulation, immune evasion, and targeting of inflamed tissues, with the many functions of engineered cores. This review systematically summarizes recent advances in the design and application of nanotherapeutics, categorizing them into three platforms: those derived from natural platelet membranes, those utilizing engineered platelet membranes for enhanced targeting or drug loading, and those employing hybrid membranes fused with other cell types to combine complementary functionalities. We emphasize their therapeutic efficacy in various inflammatory diseases such as atherosclerosis, ischemic injury (stroke and myocardial infarction), rheumatoid arthritis, microbial infections, and the tumor inflammatory microenvironment. Finally, we discuss the translational potential and current challenges of this technology and provide a critical perspective on its future development in precision medicine.

Purpose: Cancer immunotherapy aims to enhance the immune system's ability to recognize and eliminate cancer cells, providing a sustained and effective immune response. However, the tumor microenvironment (TME), characterized by an abundance of tumor-associated M2 macrophages and the presence of exhausted or naïve T cells (non-effector T cells), remains a major barrier to effective immunotherapy. Herein, inflammatory M1 macrophage-derived extracellular vesicles (M1EV) were surface-modified to display interleukin-2 (M1EV_IL2), aiming to develop a multifunctional cancer immunotherapeutic agent capable of modulating both innate and adaptive immune responses.

Methods: We engineered M1EV to label the surface with azide groups through metabolic glycoengineering and developed M1EV_IL2 that displayed IL-2 via bioorthogonal chemistry. M1EV_IL2 were purified by size-exclusion chromatography (SEC) and characterized through comprehensive analyses, including nanoparticle tracking analysis (NTA). In vitro macrophage repolarization and T cell activation were evaluated at the gene-expression level, followed by ex vivo assays assessing T-cell proliferation, cytokine secretion, and activation marker expression.

Results: M1EV_IL2 effectively retained the intrinsic physicochemical properties of EVs while displaying IL-2 stably on its surface. It upregulated M1 macrophage markers, IL-1β and CXCL10, while downregulating the M2 macrophage marker CD206, thereby inducing M2-to-M1 macrophage repolarization. In addition, M1EV_IL2 also activated CD4⁺ T cells and induced the activation of naïve CD8⁺ T cells to effector T cells, leading to enhanced cell proliferation and secretion of antitumor cytokines.

Conclusion: These results indicate that M1EV_IL2 has the potential to reshape the tumor immune landscape by simultaneously activating macrophages and T cells, thereby enhancing both innate and adaptive immune responses. Unlike conventional cancer therapies, which directly target tumor cells, M1EV_IL2 is expected to enhance immune responses, potentially mitigating adverse effects while improving therapeutic efficacy.

Background: Immune checkpoint inhibitor (ICI) therapies have marked a significant breakthrough in tumor immunotherapy. However, their clinical efficacy remains suboptimal in many cases. Emerging evidence indicates that resistance to ICIs is largely driven by the immunosuppressive nature of the tumor microenvironment (TME). Modulating the TME-through conventional chemotherapy or anti-angiogenic therapies has been shown to enhance immune activation and improve the therapeutic response to ICIs.

Methods: In this study, we developed epirubicin (EPI)-loaded lipid nanoparticles, termed DPPA(EPI) LNPs, which integrate the chemotherapeutic agent EPI with the anti-angiogenic lipid DPPA, enabling co-delivery and targeted enrichment within tumors. The cytotoxicity and anti-vascular endothelial cell tube formation properties of DPPA(EPI) LNPs were tested in vitro. The biosafety, anti-tumor ability and immunoactivities were tested on orthotopic tumor models of both breast cancer and hepatoma in vivo.

Results: DPPA(EPI) LNPs showed the advantages of uniformed particle size, high stability, good sustained-release effect. Compared to free drug, DPPA(EPI) LNPs significantly prolonged blood circulation (21.7% remaining at 12 h vs.16.5% at 30 min for free drug), enhanced tumor accumulation (18.4-fold change than free drug) and had well biological safety. In vivo, DPPA (EPI) LNPs showed excellent anti-tumor therapeutic efficacy by significantly inhibiting tumor cell proliferation (Ki67† cells reduced by 55%), reducing tumor angiogenesis (vascular density by 60%), and inducing stronger immunogenic cell death effect both in 4T1 orthotopic tumor model and Hepa1-6 orthotopic tumor model. And the treatment of DPPA (EPI) LNPs combined with programmed cell death protein 1 (PD-1) inhibitor further improved the activation of anti-tumor immunity in the TME, which leads to more significant inhibition of the tumor growth.

Conclusion: This dual-function nanoplatform-combining chemotherapy and anti-angiogenic therapy-substantially improved the efficacy of PD-1 blockade in both breast cancer and hepatocellular carcinoma (HCC) models. These findings offer a promising strategy and experimental foundation for TME modulation and the advancement of combination immunotherapy.

Carbon nanotubes (CNTs) and their composites exhibit considerable potential for application in tissue engineering, owing to their unique physical, chemical, and biological properties which render them ideal candidates for constructing biological scaffolds, facilitating tissue regeneration, and enhancing cellular functions. This review systematically examines the application of CNT-based scaffolds, with a focus on their synergistic mechanical, electrical, and bioactive properties. We discuss the fundamental characteristics of CNTs, including their mechanical strength, electrical conductivity, chemical modifiability, antimicrobial activity, and the central challenge of cytotoxicity. Strategies to mitigate cytotoxicity through functionalization and composite formation are elaborated. The review probes the enhanced biocompatibility, electrical properties, and mechanical performance of CNT composites, alongside their applications in bone, neural, and cardiac tissue engineering. A specific focus is placed on CNT scaffolds functionalized with growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), highlighting their role in promoting angiogenesis and osteogenesis. Finally, we summarize the current state of the field, address existing limitations-particularly regarding cytotoxicity and long-term safety-and suggest promising directions for future research, including the integration of photothermal therapy and the need for more comprehensive in vivo studies. This review aims to provide a balanced and critical perspective on the journey of CNT-based scaffolds from laboratory innovation to clinical reality.

Osteosarcoma and other solid tumor therapies remain urgent clinical challenges. Currently, treatment mainly relies on surgical resection. However, surgery often requires extensive removal of bone and surrounding tissues, which can easily lead to impaired limb function, affect patients' immune and metabolic functions, and increase the risk of recurrence. Smart nanomedicine offers new hope for the treatment of solid tumors. Nanoparticles can enable targeted drug delivery and personalized treatment, reduce damage to normal tissues, and help prevent dysfunction and disability. Postoperative adjuvant nanomedicines can help eliminate residual tumor cells, lower the recurrence rate, control distant metastasis, and improve survival rates. Additionally, nanoparticle-based immunotherapy has shown promising prospects. By integrating artificial intelligence and big data platforms, the development of smart nanomedicine systems can become more efficient, reliable, and tailored to the specific needs of osteosarcoma therapy. However, there are still biosafety, ethical, and regulatory challenges in clinical translation. In the future, it is necessary to further optimize the targeting and biocompatibility of nanocarriers, strengthen research on tumor metabolism, and improve regulatory systems to promote the clinical application and commercial development of multifunctional nanoparticles.