Bioreducible Polymer Nanocarrier Based on Multivalent Choline Phosphate for Enhanced Cellular Uptake and Intracellular Delivery of Doxorubicin
Bioreducible Polymer Nanocarrier Based on Multivalent Choline Phosphate for Enhanced Cellular Uptake and Intracellular Delivery of Doxorubicin
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基于多价磷酸胆碱的生物可还原聚合物纳米载体，用于增强阿霉素的细胞摄取和细胞内递送
DOI：
10.1021/acsami.7b03317
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发表时间：
2017
影响因子：
9.5
通讯作者：
Yu Xifei
中科院分区：
文献类型：
--
作者：
Wang Wenliang;Wang Bo;Liu Sanrong;Shang Xudong;Yan XinXin;Liu Zonghua;Ma Xiaojing;Yu Xifei
有限的细胞摄取和低效的细胞内药物释放严重阻碍了聚合物药物纳米载体在癌症化疗中的应用前景。在这里，为了同时应对肿瘤治疗中的这些紧迫挑战，我们将多价磷酸胆碱(CP)和生物可还原连接物整合到单一的高分子链中，设计并合成了一种新型的生物可还原聚合物纳米载体。这些两性离子CP具有良好的亲水性，使阿霉素具有较高的载药量和载药效率(∼为22.1wt%，∼为95.9%)。同时，我们发现多价磷酸胆碱能在几秒钟内有效地提高载药纳米载体的内化效率，而且提高的程度取决于单个聚合物链中的CP密度。此外，在这些纳米载体进入肿瘤细胞后，生物可还原连接体的加速切割使更多的货物可能从递送系统逃逸到细胞质中，从而更有效地发挥其细胞抑制作用。在不同细胞系中增强的治疗效果表明该系统在抗癌药物输送应用中具有巨大的潜力。
Limited cellular uptake and inefficient intracellular drug release severely hamper the landscape of polymer drug nanocarriers in cancer chemotherapy. Herein, to address these urgent challenges in tumor treatment simultaneously, we integrated the multivalent choline phosphate (CP) and bioreducible linker into a single polymer chain, designed and synthesized a neoteric bioreducible polymer nanocarrier. The excellent hydrophility of these zwitterionic CP groups endowed high drug loading content and drug loading efficiency of doxorubicin to this drug delivery system (∼22.1 wt %, ∼95.9%). Meanwhile, we found that the multivalent choline phosphate can effectively enhance the internalization efficiency of this drug-loaded nanocarrier over few seconds, and the degree of improvement depended on the CP density in a single polymer chain. In addition, after these nanocarriers entered into the tumor cells, the accelerated cleavage of bioreducible linker made it possible for more cargo escape from the delivery system to cytoplasm to exert their cytostatic effects more efficiently. The enhanced therapeutic efficacy in various cell lines indicated the great potential of this system in anticancer drug delivery applications.