 Professor 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-based 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). Through genetic engineering, the research team combined NVs carrying the membrane fusion-promoting protein VSVG with the calcium ionophore A23187 and a plasmid encoding tumor necrosis factor-α (TNF-α), creating VSVG-NVs (abbreviated as V-NVs/T+A). This design enables NVs to fuse with target cancer cells and effectively deliver TNF-α into the cells, promoting deep penetration of TNF-α in tumor tissue and reshaping 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 an EV-hitchhiking mechanism, enhancing the microenvironment to stimulate a robust immune response against cancer. To verify the effectiveness of VSVG-NVs, the researchers conducted a series of experimental studies, such as cell uptake, cell immune activation, cytotoxicity experiments, A23187 mechanism verification, intercellular transport 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 (for details, see the original literature). The results showed that V-NVs/T+A (V-NVs loaded with A23187 and TNF-α-Lamp2b plasmids) exhibited excellent stability and penetration in vitro and in vivo. The VSVG component promoted the fusion of NVs with target cancer cells and their further integration into secreted EVs. A23187 enhances EV secretion by increasing intracellular calcium levels, thereby improving the intracellular delivery of TNF-α. This effectively promoted deep tumor penetration of TNF-α and reshaped the immune microenvironment, enhancing the immune response and inhibiting 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. |
