Bioinspired Extracellular Vesicles for Enhanced Delivery of siRNA to Tumors.

Lipid nanoparticles (LNPs) are among the most effective nanocarriers for siRNA delivery due to their high transfection efficiency, nucleic acid encapsulation capacity, and relatively low toxicity. This has led to significant interest from academic institutions and pharmaceutical companies. However, the intrinsic hepatic tropism of LNPs limits their potential for targeted siRNA delivery to tumors. Extracellular vesicles (EVs), as natural nucleic acid carriers, exhibit unique biological properties. In recent years, EVs derived from M1 macrophages have gained particular attention for tumor-targeted therapy. Bioinspired nanovesicles composed of LNPs and M1 macrophage-derived EVs may combine the advantageous characteristics of both carriers and offer a promising vehicle for siRNA delivery to tumor tissues, thus warranting further investigation. This chapter outlines a laboratory-scale method for constructing bioinspired nanovesicles. First, a range of experimental methods for screening and optimizing these nanovesicles are introduced. Then, various assessment metrics such as siRNA encapsulation efficiency, vesicle fusion efficiency, and target gene silencing efficiency are discussed. Finally, experimental designs are presented for evaluating the potential siRNA delivery capabilities of these bioinspired nanovesicles both in vitro and in vivo.