荧光标记pH敏感胶束的制备及其药物控释

Preparation of Fluorescently Labeled pH-Sensitive Micelles for Controlled Drug Release

利用原子转移自由基聚合方法(ATRP)合成了pH敏感的两亲性嵌段共聚物m PEG-b-PDPA_n(聚合度n=100-200)及荧光修饰的嵌段聚合物异硫氰酸荧光素-聚乙二醇-聚N,N-二异丙胺基甲基丙烯酸乙酯(FITCPEG_(45)-PDPA_(100))。采用溶剂挥发的方法制备胶束,此胶束呈现均一的球形分布,平均粒径180-240 nm(0.3mg?m L^(-1))。以阿霉素(DOX)为模拟药物,其胶束载药量约11%(w,质量分数)左右,外环境pH对载药胶束的粒径和体外释放行为有显著影响。在弱酸环境下,胶束核质子化发生膨胀甚至解体,在2-3h内药物可释放80%左右。体外毒性试验表明,空白胶束与人类肝癌细胞(Huh7)有良好的生物相容性。同时,与此细胞共同孵育5h的荧光聚合物胶束体现了较好的转染效果。因此,这类荧光标记胶束可能会为实时跟踪化疗药物的输送或分布打开新的视角。

In this paper, novel pH-sensitive amphiphilic diblock copolymers[mPEG-b-PDPAn （n=100-200, polymerization degree; PEG is polyethylene glycol and PDPA is polydiphenylamine）] with and without a fluorescent group （fluorescein isothiocyanate, FITC） were synthesized by atom transfer radical polymerization （ATRP）. The copolymers were used to prepare micelles by solvent evaporation to act as drug carriers. The micelles were spherical with a uniform diameter of 180-240 nm （0.3 mg·mL^-1）. The model drug doxorubicin （DOX） could be encapsulated into the micelles with a high loading efficiencyof about 11% （w, mass fraction）. The micelles were stable at pH 7.4 and became looser upon the protonation of the PDPA block in a weakly acidic environment. The release of DOX accelerated when the micelles were exposed to weakly acidic conditions, and the amount released reached 80%after 2-3 h. Cell toxicity assays of the micelles were carried out using human cancer cells （Huh7）, and the micelles showed good cytocompatibility. The micelles labeled with FITC displayed high cell transfection efficiency. As a result, micelles labeled with fluorescent groups may open up new perspectives for real-time tracking of drug delivery and/or distribution during chemotherapy.