Construction of Aptamer‐siRNA Chimera/PEI/5‐FU/Carbon Nanotube/Collagen Membranes for the Treatment of Peritoneal Dissemination of Drug‐Resistant Gastric Cancer

Abstract Due to extensive metastasis, poor blood supply, and drug‐resistant, there is still no effective clinical means to treat peritoneal dissemination of gastric cancer. Here, an aptamer‐siRNA chimera (Chim)/polyethyleneimine (PEI)/5‐fluorouracil (5‐FU)/carbon nanotube (CNT)/collagen membrane is constructed, which could be divided into 15 layers with a thickness of 70–100 µm. Sustained release experiments show that the collagen membranes can control 5‐FU release for more than 2 weeks. Aptamer‐siRNA chimera can specifically bind to gastric cancer cells, enabling targeted delivery of 5‐FU and silencing drug‐resistant gene. In vitro experiments demonstrated that Chim/PEI/5‐FU/CNT nanoparticles promoted the apoptosis of 5‐FU‐resistant gastric cancer cells, inhibited their invasion and proliferation. Animal experiments show that Chim/PEI/5‐FU/CNT/collagen membrane significantly inhibits the expression of mitogen‐activated protein kinase (MAPK), and effectively treats peritoneal dissemination of 5‐FU‐resistant gastric cancer. Compared with siRNA/PEI/5‐FU/CNT group, ki‐67 proliferation index, and matrix metallopeptidase 9 (MMP9) expression are significantly decreased in the Chim/PEI/5‐FU/CNT group, while the proportion of apoptotic cells is markly increased. In conclusion, a chimera/PEI/5‐FU/CNT/collagen membrane is constructed, which can effectively treat peritoneal dissemination of drug‐resistant gastric cancer. The study provides a new therapeutic approach for relevant clinical treatment.