College of Polymer Science and Engineering of Sichuan University, Sichuan University, Chengdu 610065, China.
J Biomed Nanotechnol. 2013 Nov;9(11):1847-61. doi: 10.1166/jbn.2013.1686.
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)-r-poly(N-(3-sulfopropyl)-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 (1HNMR). The poly(N-(3-sulfopropyl)-N-methacryloxyethy-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 x HCl). These pH-sensitive micelles are potential promising carriers for anti-cancer drug delivery.
pH 敏感胶束被认为是一种很有前途的肿瘤靶向药物载体。在这项研究中，设计并合成了一种新型 pH 敏感星型两亲性嵌段共聚物聚（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-甲基丙烯酰氧基乙基-N，N-二乙基铵甜菜碱）（4sPCLDEAS），其是通过开环聚合（ROP）和原子转移自由基聚合（ATRP）相结合得到的。共聚物的结构通过质子核磁共振谱（1HNMR）进行了表征。聚（N-（3-磺丙基）-N-甲基丙烯酰氧基乙基-N，N-二乙基铵甜菜碱）段被用作共聚物中的亲水嵌段，取代了聚乙二醇（PEG），以形成聚合物胶束。胶束呈现球形，粒径分布较窄，并对酸度有响应。胶束的 CMC 低至 1 x 10(-3)mg mL(-1)。阿霉素（DOX）能够有效地包封在胶束中，并且药物释放具有 pH 依赖性。研究了胶束的细胞毒性和细胞内药物递送。胶束对人宫颈癌（Hela）细胞无毒性。载药胶束能够有效地被 Hela 细胞内化，其效果优于亲水性盐酸阿霉素（DOX x HCl）。这些 pH 敏感胶束是一种很有前途的抗癌药物载体。
