Anti-HER-2-modified exosomes loaded with siRNA-STIL specifically target and inhibit the development and progression of gastric cancer

STIL is a key molecule influencing the proliferation and cell cycle of gastric cancer cells; however, STIL is also expressed in normal tissues. Therefore, designing a drug delivery system that targets gastric cancer cells is crucial for STIL-targeted therapy. In this study, we constructed exosomes targeting the HER-2 receptor and loaded with siSTIL (Anti-HER-2-Exo-siSTIL), and validated the inhibitory effects of Anti-HER-2-Exo-siSTIL on gastric cancer proliferation and metastasis in vivo. Anti-HER-2-Exo-siSTIL was able to enter SGC-7901 cells and inhibit STIL expression, significantly suppressing the growth of SGC-7901 xenograft tumors. By downregulating STIL and the anti-apoptotic protein Bcl-2, and upregulating the pro-apoptotic proteins Bax, Caspase-3, and Caspase-9, Anti-HER-2-Exo-siSTIL effectively induced apoptosis in tumor cells. Furthermore, Anti-HER-2-Exo-siSTIL selectively inhibited lung metastasis of SGC-7901 cells via hematogenous dissemination. In summary, Anti-HER-2-Exo-siSTIL specifically targets and suppresses gastric cancer proliferation and lung metastasis, demonstrating its significant translational potential for gastric cancer therapy.