Delivery of TSPAN1 siRNA by Novel Th17 Targeted Cationic Liposomes for Gastric Cancer Intervention

Several studies focus on the relationship between immune cells in the tumor microenvironment and tumor cells. Th17 cells, a naïve CD4⁺ T cell subtype, secrete IL-17 cytokines that further the progression and metastasis of tumors, such as gastric cancer, which is a leading cause of cancer-related death worldwide. Moreover, previous studies have demonstrated that the polarization ratio of CD4⁺ T cells to Th17 cells is closely related to the Tetraspanin 1 (TSPAN1) protein. Therefore, in this study, we designed a novel Th17 antibody-modified liposome polycation-DNA complex (LPD) encapsulated with TSPAN1 small interfering RNA (siRNA) (Th17-LPDT), to decrease the polarization of CD4⁺ T cells, and thereby inhibit the development of gastric cancer. Our in vitro results demonstrated the decrease in CD4⁺ T cells polarization to Th17 cells follwing Th17-LPDT treatment. Furthermore, in vivo data proved that Th17-LPDT treatment significantly inhibits the formation of gastric tumors. We believe that Th17-LPDT is a promising targeted nanoparticle drug for the clinical treatment of gastric cancer and this study provides a new strategy for tumor intervention.