 Mr. Sun Jin from Shenyang Pharmaceutical University The team recently "Nano Today" (IF: 13.2) The article "Engineered cytomembrane nanovesicles trigger in situ storm of engineered extracellular vesicles for cascade tumor penetration and immune microenvironment remodeling" was published on Qihengxing's flagship product FS-Q1005 (StarLighter high-performance dye method qPCR premix (universal)) I am fortunate to be able to participate in this and contribute to this research! 
This study is about a new type of nanocarrier - engineered cytomembrane nanovesicles (NVs), which are designed to enhance immunotherapy for triple-negative breast cancer (TNBC). The research team used genetic engineering to combine NVs carrying the membrane fusion-promoting protein VSVG with the calcium ion carrier A23187 and a plasmid encoding tumor necrosis factor-α (TNF-α) to form VSVG-NVs (V-NVs/T+A for short). This design enables NVs to fuse with target cancer cells and effectively deliver TNF-α into the cells, promoting the deep penetration of TNF-α in tumor tissues and the remodeling of the immune microenvironment (Figure 1).  Figure 1. Preparation of fusogenic cell membrane nanovesicles and their biological functions. Note: The innovative fusion nanovesicle platform V-NVs/T+A integrates A23187 and TNF-α-Lamp2b plasmids, ensuring precise intracellular targeting while avoiding lysosomal clearance. This sophisticated design promotes deep tumor penetration through the EV-hitchhiking mechanism and enhances the microenvironment to stimulate a strong immune response against cancer. In order to verify whether VSVG-NVs are effective, the researchers conducted a series of experimental studies, such as cell uptake, cell immune activation, cytotoxicity experiments, A23187 mechanism verification, intercellular transmission mechanism verification, tumor spheroid penetration efficiency, animal experiments, in vivo pharmacokinetics and distribution, in vivo penetration experiments, in vivo anti-metastasis performance and in vivo anti-tumor evaluation (see the original text for details). The results showed that V-NVs/T+A (V-NVs loaded with A23187 and TNF-α-Lamp2b plasmids) showed good stability and penetration in in vitro and in vivo experiments. The VSVG component promoted the fusion of NVs with target cancer cells and further integrated into secreted EVs. A23187 enhances the secretion of EVs by increasing the intracellular calcium ion level, thereby improving the intracellular delivery efficiency of TNF-α, which can effectively promote the deep tumor penetration of TNF-α and the remodeling of the immune microenvironment, enhance the immune response, and inhibit tumor growth and metastasis. In conclusion, this article provides a novel therapeutic strategy to enhance immune responses through NVs-mediated deep penetration of TNF-α, offering a new approach to overcome the barriers of immunotherapy in cold tumors. |
