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.

中文翻译：

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适配体-siRNA嵌合体/PEI/5-FU/碳纳米管/胶原膜的构建用于治疗耐药胃癌的腹膜播散。

由于胃癌转移广泛、血供差、耐药等特点，目前临床上尚无有效治疗胃癌腹膜播散的手段。在这里，构建了适体-siRNA嵌合体（Chim）/聚乙烯亚胺（PEI）/5-氟尿嘧啶（5-FU）/碳纳米管（CNT）/胶原膜，可分为15层，厚度为70-100微米。缓释实验表明，胶原膜可以控制 5-FU 释放 2 周以上。Aptamer-siRNA 嵌合体可特异性结合胃癌细胞，实现 5-FU 的靶向递送和耐药基因沉默。体外实验表明，Chim/PEI/5-FU/CNT 纳米粒子促进 5-FU 耐药胃癌细胞的凋亡，抑制其侵袭和增殖。动物实验表明，Chim/PEI/5-FU/CNT/胶原膜显着抑制丝裂原活化蛋白激酶（MAPK）的表达，有效治疗5-FU耐药胃癌的腹膜播散。与siRNA/PEI/5-FU/CNT组相比，Chi-67增殖指数、基质金属肽酶9（MMP9）表达在Chim/PEI/5-FU/CNT组中显着降低，而凋亡细胞比例降低明显增加。综上所述，构建了嵌合体/PEI/5-FU/CNT/胶原膜，可有效治疗耐药胃癌腹膜播散。该研究为相关临床治疗提供了一种新的治疗途径。并有效治疗 5‐FU 耐药胃癌的腹膜播散。与siRNA/PEI/5-FU/CNT组相比，Chi-67增殖指数、基质金属肽酶9（MMP9）表达在Chim/PEI/5-FU/CNT组中显着降低，而凋亡细胞比例降低明显增加。综上所述，构建了嵌合体/PEI/5-FU/CNT/胶原膜，可有效治疗耐药胃癌腹膜播散。该研究为相关临床治疗提供了一种新的治疗途径。并有效治疗 5‐FU 耐药胃癌的腹膜播散。与siRNA/PEI/5-FU/CNT组相比，Chi-67增殖指数、基质金属肽酶9（MMP9）表达在Chim/PEI/5-FU/CNT组中显着降低，而凋亡细胞比例降低明显增加。综上所述，构建了嵌合体/PEI/5-FU/CNT/胶原膜，可有效治疗耐药胃癌腹膜播散。该研究为相关临床治疗提供了一种新的治疗途径。构建了嵌合体/PEI/5-FU/CNT/胶原膜，可有效治疗耐药胃癌腹膜播散。该研究为相关临床治疗提供了一种新的治疗途径。构建了嵌合体/PEI/5-FU/CNT/胶原膜，可有效治疗耐药胃癌腹膜播散。该研究为相关临床治疗提供了一种新的治疗途径。