College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China.
College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China; State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
Colloids Surf B Biointerfaces. 2020 May;189:110741. doi: 10.1016/j.colsurfb.2019.110741. Epub 2020 Feb 1.
There are opportunities for improvements to the efficiency and toxicity of widely used cancer chemotherapy agents such as doxorubicin (DOX·HCl) and 7-Ethyl-10-hydroxycamptothecin (SN38). We developed a safe and effective combination therapy by encapsulating DOX into micelles of a zwitterionic polymer prodrug, SN38 conjugate of poly (α-azide caprolactone-co-caprolactone)-b-poly (2-methacryloyloxyethyl phosphorylcholine [P(CL/CL-g-SN38)-b-PMPC)] which was described in our previous work. The polymer prodrug micelles displayed a higher loading capacity of DOX due to the π-π stacking effect between DOX and SN38 in comparison with the micelles self-assembled by prodrug's precursor, poly(α-azide caprolactone-co-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine (P(ACL/CL)-b-PMPC). The DOX loaded prodrug micelles decelerated the release of DOX, and also prolonged its circulation. The micelles showed favorable cellular internalization by 4T1 cells. DOX loaded SN38 prodrug micelles displayed good in vitro anticancer effects owing to the synergistic action of doxorubicin and SN38 and were as effective as DOX·HCl, but with lower toxicity than DOX·HCl. Given the synergetic effects of free drug and polymer prodrug, this nanomedicine may offer a safe and effective drug delivery methodology for conventional drug formations.
有机会提高广泛使用的癌症化疗药物如多柔比星（DOX·HCl）和 7-乙基-10-羟基喜树碱（SN38）的效率和毒性。我们通过将 DOX 包封在两性离子聚合物前药 SN38 缀合物的胶束中，开发了一种安全有效的组合疗法，该前药是我们之前工作中描述的聚（α-叠氮己内酯-co-己内酯）-b-聚（2-甲基丙烯酰氧乙基磷酸胆碱[P（CL/CL-g-SN38）-b-PMPC)]。与前药的前驱体自组装的胶束相比，聚合物前药胶束由于 DOX 和 SN38 之间的π-π堆积作用而具有更高的 DOX 载药量，聚（α-叠氮己内酯-co-己内酯）-b-聚（2-甲基丙烯酰氧乙基磷酸胆碱[P（ACL/CL）-b-PMPC)]。载 DOX 的前药胶束减缓了 DOX 的释放，并延长了其循环。胶束通过 4T1 细胞表现出良好的细胞内化。载 DOX 的 SN38 前药胶束由于阿霉素和 SN38 的协同作用显示出良好的体外抗癌作用，与 DOX·HCl 一样有效，但毒性低于 DOX·HCl。鉴于游离药物和聚合物前药的协同作用，这种纳米药物可能为常规药物制剂提供一种安全有效的药物递送方法。
