In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4–siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox–siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4–siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment.

中文翻译：

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具有双pH /氧化还原敏感性的靶向Nucleolin的AS1411-适体修饰的接枝聚合物胶束，旨在通过阿霉素/ TLR4 siRNA的代码传递和抑制入侵来增强肿瘤治疗。

在本文中，合成了具有适体AS1411的靶向功能的新型接枝聚合物胶束。胶束基于壳聚糖-ss-聚乙烯亚胺-尿酸（CPU），具有双重pH /氧化还原敏感性和靶向作用。产生该胶束的目的是将Toll样受体4 siRNA（TLR4–siRNA）和阿霉素（Dox）编码递送。体外研究表明，在生理条件下，从装载Dox–siRNA的胶束中可以持续释放基因和药物，并且该代码传递纳米系统显示出高的pH /氧化还原双重敏感性，快速的细胞内药物释放以及改善的针对A549细胞的体外细胞毒性。此外，载有TLR4-siRNA的胶束抑制了A549的迁移和侵袭。在A549肿瘤球体和实体肿瘤切片中也注意到了极好的肿瘤穿透功效。在体内，多项结果证明AS1411-壳聚糖-ss-聚乙烯亚胺-尿酸（ACPU）胶束在肿瘤组织中具有出色的肿瘤靶向能力。胶束在携带肺肿瘤的BALB / c小鼠的全身循环中表现出优异的抗肿瘤功效和低毒性。这些结果最终证明了具有靶向功能的新型接枝共聚物胶束在化疗药物和基因的靶向有效治疗中具有巨大的潜力。