SATB1 siRNA-encapsulated immunoliposomes conjugated with CD44 antibodies target and eliminate gastric cancer-initiating cells

PURPOSE: Gastric cancer, the cancer initiated from the stomach, is ranked as the third most frequent reason of cancer death worldwide. Gastric cancer-initiating cells (CICs) are one of the crucial causes for the metastasis and recurrence of gastric cancer, and CD44 is considered to be one marker for gastric CICs. Special AT-rich sequence binding protein 1 (SATB1) is a protein that promotes cancer progression, metastasis, and invasion and also participates in the maintenance of CICs. In this study, we investigated the therapeutic effect of SATB1 siRNA against gastric CICs and we constructed SATB1 siRNA-encapsulated immunoliposomes conjugated with CD44 antibodies (CD44-SATB1-ILs) to enhance the therapeutic effect of SATB1 siRNA against gastric CICs. METHODS: We investigated the therapeutic effect of the SATB1 suppression by SATB1 siRNA on CD44(+) gastric CICs. CD44-SATB1-ILs were developed by the lyophilization/hydration approach. The targeting and cytotoxic effect of CD44-SATB1-ILs toward gastric CICs were evaluated in vitro. RESULTS: In this study, for the first time, we confirmed that SATB1 suppression by SATB1 siRNA preferentially eliminated CD44(+) gastric CICs. The results showed that CD44-SATB1-ILs could efficiently and specifically promote the SATB1 siRNA delivery to CD44(+) gastric CICs, achieving superior therapeutic effects against CD44(+) gastric CICs than non-targeted liposomes. CONCLUSION: As far as we know, our report is the first research that indicated the promotion of siRNA delivery via nanoparticles to gastric CICs and achievement of superior therapeutic effect against gastric CICs by utilization of CD44 antibody. Therefore, CD44-SATB1-ILs represent an up-and-coming approach for eliminating gastric CICs and also a promising treatment for therapy of gastric cancer.