Modified polyethyleneimine (PEI) has been widely used as siRNA delivery agents. Here, a new Triton X-100-modified low-molecular-weight PEI siRNA delivery agent is developed together with the coupling of 4-carboxyphenylboronic acid (PBA) and dopamine grafted vitamin E (VEDA). Triton X-100, a nonionic detergent, greatly improves the cellular uptake of siRNA as well as the siRNA escape from endosome/lysosome because of its high transmembrane ability. In addition, the boronate bond between PBA and VEDA of the transfection agent can be triggered to release its entrapped siRNA because of the high level of adenosine triphosphate (ATP) in cancer cells. The transfection agent is successfully applied to deliver siRNAs targeting endogenous genes of epidermal growth factor receptor (EGFR) and kinesin-5 (Eg5) to cancer cells, showing good results on Eg5 and EGFR silencing ability and inhibition of cancer cell migration. Further in vivo study indicates that the Triton X-100-modified transfection agent is also efficient to deliver siRNA to cancer cells and shows significant tumor growth inhibition on mice tumor models. These results indicate that the Triton X-100-modified ATP-responsive transfection agent is a promising gene delivery vector for target gene silencing in vitro and in vivo.

中文翻译：

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用于抗肿瘤治疗的 Triton X-100 修饰的三磷酸腺苷响应性 siRNA 递送剂。

改性聚乙烯亚胺 (PEI) 已被广泛用作 siRNA 递送剂。在这里，与 4-羧基苯基硼酸 (PBA) 和多巴胺接枝维生素 E (VEDA) 的偶联一起开发了一种新的 Triton X-100 修饰的低分子量 PEI siRNA 递送剂。Triton X-100 是一种非离子去污剂，由于其高跨膜能力，大大提高了 siRNA 的细胞摄取以及 siRNA 从内体/溶酶体中的逃逸。此外，由于癌细胞中高水平的三磷酸腺苷 (ATP)，可以触发转染剂的 PBA 和 VEDA 之间的硼酸酯键以释放其捕获的 siRNA。该转染剂成功应用于将靶向表皮生长因子受体 (EGFR) 和驱动蛋白-5 (Eg5) 内源基因的 siRNA 递送至癌细胞，在 Eg5 和 EGFR 沉默能力和癌细胞迁移抑制方面显示出良好的结果。进一步的体内研究表明，Triton X-100 修饰的转染剂还可以有效地将 siRNA 传递给癌细胞，并对小鼠肿瘤模型显示出显着的肿瘤生长抑制作用。这些结果表明 Triton X-100 修饰的 ATP 响应性转染剂是一种有前途的基因递送载体，可用于体外和体内靶基因沉默。