Novel pH-Sensitive Micelles Generated by Star-Shape Copolymers Containing Zwitterionic Sulfobetaine for Efficient Cellular Internalization
Novel pH-Sensitive Micelles Generated by Star-Shape Copolymers Containing Zwitterionic Sulfobetaine for Efficient Cellular Internalization
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由含有两性离子磺基甜菜碱的星形共聚物生成的新型 pH 敏感胶束，可实现有效的细胞内化
DOI：
10.1166/jbn.2013.1686
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发表时间：
2013-11-01
影响因子：
2.9
通讯作者：
Gu, Zhongwei
中科院分区：
文献类型：
--
作者：
Cao, Jun;Zhai, Shuying;Gu, Zhongwei
pH敏感性胶束被认为是肿瘤靶向给药的有前途的载体。本研究采用开环聚合（ROP）和原子自由基转移聚合（ATRP）相结合的方法，设计并合成了新型的两亲性星形共聚物聚（ε-己内酯）-b-聚（N，N-二乙基氨基乙基甲基丙烯酸酯）-r-聚（N-（3-磺丙基）-N-甲基丙烯酰氧乙基-N，N-二乙基铵甜菜碱）（4sPCLDEAS）。用核磁共振氢谱（HNMR）-H-1表征了共聚物的结构。用聚（N-（3-磺丙基）-N-甲基丙烯酰氧乙基-N，N-二乙基铵甜菜碱）链段代替聚乙二醇（PEG）作为亲水性嵌段，形成聚合物胶束。胶束呈球形，粒径分布窄，对酸度有较好的响应性。胶束的CMC低至1 × 10（-3）mg/mL（-1）。阿霉素（DOX）被有效地包裹在胶束中，药物释放是pH依赖性的。研究了胶束的细胞毒性和细胞内药物释放。该胶束对人宫颈癌（Hela）细胞无毒性。阿霉素胶束在Hela细胞中的内化效率高于亲水性盐酸阿霉素（DOX HCl）。这些pH敏感胶束是一种潜在的抗癌药物载体。
pH-sensitive micelles are considered promising carriers for tumor targeted drug delivery. In this study, novel pH-sensitive star-shape copolymers of amphiphilic poly(epsilon-caprolactone)-b-poly(N, N-diethylaminoethyl methacrylate)-rpoly(N-(3-sulfopropy1)-N-methacryloxyethy-N, N-diethylammoniumbetaine) (4sPCLDEAS) are designed and synthesized with the combination of ring opening polymerization (ROP) and atom radical transferpolymerization (ATRP). The structure of the copolymers is characterized by proton nuclear magnetic resonance spectra ((HNMR)-H-1). The poly(N-(3-sulfopropyI)-Nmethacryloxyethy-N, N-diethylammoniumbetaine) segment is used instead of poly(ethylene glycol) (PEG) as hydrophilic block in the copolymers to form polymeric micelles. The micelles present spherical shape, narrow size distribution, and are reponsive to the acidity. The CMC of the micelles is as low as 1 x 10(-3) mg mL(-1). Doxorubin (DOX) is efficiently encapsulated in the micelles and the drug release is pH dependant. The cytotoxicity as well as the intracellular drug delivery of the micelles are investigated. The micelles are nontoxic to human cervical carcinoma (Hela) cells. The DOX-loaded micelles are internalized in Hela cells efficiently, which are better than that of hydrophilic doxorubicin hydrochloride (DOX HCI). These pH-sensitive micelles are potential promising carriers for anti-cancer drug delivery.