摘要
Targeted drug delivery coupled with rapid drug release in cytoplasm is a powerful strategy to enhance efficacy and reduce off-target effects of anti-cancer drugs. Herein, we describe a dual-functional mixed micellar system consisting of a pH-responsive copolymer D-α-tocopheryl polyethylene glycol 1000-block- poly-（β-amino ester） （TPGS-b-PBAE, TP） and AS1411 aptamer （Apt） decorated TPGS polymer （Apt-TPGS）, which recognizes the over-expressed nucleolin on the plasma membrane of cancer cells. The anti-cancer drug paclitaxel （PTX） was encapsulated in the Apt-mixed micelles, and these drug-loaded micelles had a suitable particle size and zeta potential of 116.3 nm ± 12.4 nm and -26.2 mV ±4.2 mV, respectively. PTX/Apt-mixed micelles were stable at pH 7.4, but they dissociated and quickly released the encapsulated PTX in a weakly acidic environment （pH 5.5）. Compared with non-Apt modified mixed micelles, more Apt-modified mixed micelles were internalized in SKOV3 ovarian cancer cells, whereas no significant difference in cellular uptake was observed in normal cells （LO2 cells）. The enhanced transmembrane ability of Apt-modified mixed micelles was achieved through Apt-nucleolin interaction. With a synergistic effect of cancer cell recognition and pH-sensitive drug release, we observed significantly increased cytotoxicity and G2/M phase arrest against SKOV3 cells by PTX/ Apt-mixed micelles. Intravenous administration of PTX/Apt-mixed micelles for 16 days significantly increased tumor accumulation of PTX, inhibited tumor growth, and reduced myelosuppression on tumor-bearing mice compared with free PTX injection. Therefore, this dual-functional Apt-mixed micellar system is a promising drug delivery system for targeted cancer therapy.
结合的指向的药交货在细胞质的快速的药版本是强大的策略提高反癌症药的功效和还原剂离开目标效果。此处，我们描述由 pH 应答的共聚物 D 组成的一个双功能的混合 micellar 系统 -- tocopheryl 聚乙烯乙二醇 1000-blockpoly-( 氨基的酉旨)(TPGS-b-PBAE， TP ) 并且 AS1411 aptamer (恰当) 装饰了 TPGS 聚合物(Apt-TPGS ) ，它在癌症房间的血浆膜上认出过去表示的 nucleolin。反癌症药 paclitaxel (PTX ) 在恰当混合的微粒被包含，并且这些装载药的微粒有一种合适的粒子尺寸和 116.3 nm eir single-crystalline-like 的希腊语的第六个字母潜力远程的电子连接， VN MCNS 交付 1.44 的电的传导性 ??? 汰獵瀭畬 ?? ￣吗？
