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

J Pharm Sci. 2020 Sep;109(9):2854-2860. doi: 10.1016/j.xphs.2020.05.018. Epub 2020 Jun 1.

Abstract

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.

Keywords: Gastric cancer; Liposome; TSPAN1; Th17; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations
  • Humans
  • Liposomes*
  • RNA, Small Interfering
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Tetraspanins / genetics
  • Th17 Cells
  • Tumor Microenvironment

Substances

  • Cations
  • Liposomes
  • RNA, Small Interfering
  • TSPAN1 protein, human
  • Tetraspanins