Precise engineering of cholesterol-loaded chitosan micelles as a promising nanocarrier system for co-delivery drug-siRNA for the treatment of gastric cancer therapy

Abstract

Anticancer therapy involving chemotherapeutic drugs and therapeutic small interfering RNA (siRNA) in cancer cell lines that improves cell-killing ability and reduces side effects compared with the existing therapeutics is encouraging. However, simultaneous delivery to tumor is challenging. In this study, the self-assembled strategic delivery of the therapeutic drug salinomycin (SAL) and siRNA to cancer cells was demonstrated. Chitosan is a popular choice in the application as a drug delivery carrier due to its biocompatibility, chemical versatility, aqueous solubility, and low cost. Cholesterol-loaded chitosan nanoparticles (C) with SAL (C-SAL and siRNA@C-SAL) were physically and chemically characterized using the particle size and zeta potential. The siRNA@C-SAL has been effectively considered in a time-dependent manner by human gastric cells SNU-668 and SGC-791. The siRNA@C-SAL displayed superior in vitro cytotoxicity against two gastric carcinoma cells (SNU-668 and SGC-791). Toxicity studies using healthy mice revealed that the use of siRNA@C-SAL did not cause any significant adverse effects, whereas bare drugs caused considerable organ damage. Furthermore, the in vivo antitumor efficacy of siRNA@C-SAL was demonstrated in SNU-668 tumor-bearing mice, and no weight loss was observed in mice. Moreover, antitumor effectiveness was evaluated using hematoxylin and eosin staining. Therefore, the proposed combination therapy using an improved drug delivery system with siRNA and hydrophobic drugs provides a potential strategy for the treatment of gastric cancer.