College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Ministry of Education (MOE) Key Laboratory of Macromolecular Synthesis & Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou 310027, PR China.
Nanomedicine (Lond). 2018 Aug;13(16):2051-2066. doi: 10.2217/nnm-2018-0048. Epub 2018 Sep 6.
To meet the requirements on both delivery stability during blood circulation and fast intracellular release for water-soluble chemotherapeutics encapsulated in polymersomes.
MATERIALS & METHODS: A shell photo-crosslinked and esterase-sensitive polymersome (C-PEAMP-D) was constructed based on amphiphilic polyphosphazene PEAMP containing 2-aminoethyl methacrylate.
The leakage of doxorubicin hydrochloride (DOX·HCl) was significantly inhibited from 42.27 to 26.64% in 10 h and the accelerated intracellular DOX·HCl release occurred responsively to the esterase at high concentration in cancer cells. Consequently, C-PEAMP-D achieved better antitumor efficiency when compared with free DOX·HCl and uncrosslinked PEAMP vesicle.
We provided a strategy to conquer drug leakage in systemic circulation and trigger enzyme-sensitive drug release inside cancer cells for improving oncotherapy outcome of water-soluble chemotherapeutics.
满足载于聚合物囊泡中的水溶性化疗药物在血液循环过程中输送稳定性和快速细胞内释放的要求。
基于含有 2-氨基乙基甲基丙烯酸酯的两亲性聚膦腈 PEAMP 构建了壳层光交联和酯酶敏感聚合物囊（C-PEAMP-D）。
盐酸阿霉素（DOX·HCl）的泄漏从 10 小时的 42.27%显著抑制到 26.64%，并且在癌细胞中高浓度的酯酶作用下，加速了细胞内 DOX·HCl 的释放。因此，与游离 DOX·HCl 和未交联的 PEAMP 囊泡相比，C-PEAMP-D 实现了更好的抗肿瘤效果。
我们提供了一种策略来克服水溶性化疗药物在全身循环中的药物泄漏，并在癌细胞内触发酶敏感药物释放，以提高肿瘤治疗的效果。
