Biomembrane nanostructures: Multifunctional platform to enhance tumor chemoimmunotherapy via effective drug delivery.

Chemotherapeutic drugs have been found to activate the immune response against tumors by inducing immunogenic cell death, in addition to their direct cytotoxic effects toward tumors, therefore broadening the application of chemotherapy in tumor immunotherapy. The combination of other therapeutic strategies, such as phototherapy or radiotherapy, could further strengthen the therapeutic effects of immunotherapy. Nanostructures can facilitate multimodal tumor therapy by integrating various active agents and combining multiple types of therapeutics in a single nanostructure. Biomembrane nanostructures (e.g., exosomes and cell membrane-derived nanostructures), characterized by superior biocompatibility, intrinsic targeting ability, intelligent responsiveness and immune-modulating properties, could realize superior chemoimmunotherapy and represent next-generation nanostructures for tumor immunotherapy. This review summarizes recent advances in biomembrane nanostructures in tumor chemoimmunotherapy and highlights different types of engineering approaches and therapeutic mechanisms. A series of engineering strategies for combining different biomembrane nanostructures, including liposomes, exosomes, cell membranes and bacterial membranes, are summarized. The combination strategy can greatly enhance the targeting, intelligence and functionality of biomembrane nanostructures for chemoimmunotherapy, thereby serving as a stronger tumor therapeutic method. The challenges associated with the clinical translation of biomembrane nanostructures for chemoimmunotherapy and their future perspectives are also discussed.

Treatment with Mesenchymal Stem Cell-Derived Nanovesicle-Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization.

Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell (MSC)-derived exosomes is a promising therapeutic strategy in osteoarthritis treatment. However, the poor yield of exosomes is an obstacle to the use of this modality in the clinic. Herein, a promising strategy is developed to fabricate high-yield exosome-mimicking MSC-derived nanovesicles (MSC-NVs) with enhanced regenerative and anti-inflammatory capabilities. MSC-NVs are prepared using an extrusion approach and are found to increase chondrocyte and human bone marrow MSC differentiation, proliferation, and migration, in addition to inducing M2 macrophage polarization. Furthermore, gelatin methacryloyl (GelMA) hydrogels loaded with MSC-NVs (GelMA-NVs) are formulated, which exhibit sustained release of MSC-NVs and are shown to be biocompatible with excellent mechanical properties. In a mouse osteoarthritis model constructed by surgical destabilization of the medial meniscus (DMM), GelMA-NVs effectively ameliorate osteoarthritis severity, reduce the secretion of catabolic factors, and enhance matrix synthesis. Furthermore, GelMA-NVs induce M2 macrophage polarization and inflammatory response inhibition in vivo. The findings demonstrate that GelMA-NVs hold promise for osteoarthritis treatment through modulation of chondrogenesis and macrophage polarization.