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Codelivery of DOX and siRNA by folate-biotin-quaternized starch nanoparticles for promoting synergistic suppression of human lung cancer cells

机译:叶酸-生物素-季铵化淀粉纳米粒对DOX和siRNA的共递递促进人肺癌细胞的协同抑制

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摘要

In this paper, the self-assembled folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as carrier system of doxorubicin (DOX) and siRNAIGF1R for the codelivery of both into human lung adenocarcinoma cell lines (A549 cells) in vitro. The cytotoxicity, targeted ligand competition, cell proliferation inhibition, cellular uptake, endocytosis mechanism and target protein suppression of drug-loaded FBqS NPs were evaluated in detail. Compared with several other drug formulations under same condition, siRNAIGF1R/DOX/FBqS NPs exhibited the greatest cytotoxicity to A549 cells and the cytotoxicity was competitively inhibited by free folate in dose-dependent manner. The A549 cells treated by siRNAIGF1R/DOX/FBqS NPs showed the lowest cell proliferation capacity. The energy-dependent clathrin- and caveolae-mediated endocytosis might be the primary cellular uptake mechanism of drug-loaded FBqS NPs. The expression of IGF1R protein in A549 cells treated by siRNAIGF1R/FBqS NPs declined dramatically. So the FBqS NPs were expected as the co-carrier system of chemotherapeutants and siRNAs for future clinical application.
机译:本文以自组装的叶酸-生物素季铵化淀粉纳米颗粒(FBqS NPs)为载体,用阿霉素(siRNA)和siRNA IGF1R 共同转运至人肺腺癌细胞系。 (A549细胞)体外。详细评估了载药FBqS NPs的细胞毒性,靶向配体竞争,细胞增殖抑制,细胞摄取,内吞机制和靶蛋白抑制。与相同条件下的其他几种药物制剂相比,siRNA IGF1R / DOX / FBqS NPs对A549细胞具有最大的细胞毒性,而叶酸以剂量依赖的方式竞争性地抑制了细胞毒性。 siRNA IGF1R / DOX / FBqS NPs处理的A549细胞表现出最低的细胞增殖能力。能量依赖性网格蛋白和小窝介导的内吞作用可能是载药FBqS NPs的主要细胞摄取机制。 siRNA IGF1R / FBqS NPs处理的A549细胞中IGF1R蛋白的表达急剧下降。因此,FBqS NPs有望作为化学治疗剂和siRNA的共载体系统,以备将来临床应用。

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