Precise Targeting Therapy of Orthotopic Gastric Carcinoma by siRNA and Chemotherapeutic Drug Codelivered in pH-Sensitive Nano Platform.

Gastric cancer is one of the most common malignant tumors, which remains as an obstacle to human health. Nowadays, targeted nanoparticles to gastric tumor tissues, provide new strategy for improved therapy but still remain challenging. The major hurdle of targeted therapeutic nanoparticles comes from the limited enrichment and poor selectivity of therapeutic agents in in situ tumor. Herein, a pH-sensitive targeted nano platform coloaded As2 O3 and human epidermal growth factor receptor-2 (HER2)-siRNA (AH RNPs) is developed to achieve targeting therapy in orthotopic gastric carcinoma. AH RNPs can effectively prevent the degradation of siRNA and overcome the poor solubility of As2 O3 . In vitro studies show that AH RNPs could achieve synergistic inhibition of growth and metastasis on SGC7901 cells. Surprisingly, AH RNPs not only target gastric subcutaneous tumor, but also target in situ tumor, and express loaded genes in in situ tumor. Moreover, AH RNPs show excellent antitumor effect in orthotopic gastric tumor model and the anticancer mechanism is related about inhibiting the activation of ERK signal and downregulating the expression of cxc chemokine receptor 4 (CXCR4), HER2, MMP2, and MMP9 protein. This study provides a multi-functional vector for precise targeting therapy of gastric cancer, which may serve as a potential clinical application for future gastric cancer.