Synthesis and characterization of transferrin-targeted chemotherapeutic delivery systems prepared via RAFT copolymerization of high molecular weight PEG macromonomers.
Synthesis and characterization of transferrin-targeted chemotherapeutic delivery systems prepared via RAFT copolymerization of high molecular weight PEG macromonomers.
复制标题
通过高分子量PEG巨粒子体的筏共聚制备的转铁蛋白靶向化学治疗递送系统的合成和表征。
DOI：
10.1039/c3py01404e
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发表时间：
2014-03-07
影响因子：
4.6
通讯作者：
Convertine AJ
中科院分区：
文献类型：
--
作者：
Roy D;Berguig GY;Ghosn B;Lane D;Braswell S;Stayton PS;Convertine AJ
采用可逆加成-断裂链转移（RAFT）聚合法制备了一种用于化疗药物的纳米粒给药系统。纳米颗粒含有PEG“隐形”冠以及设计用于缀合靶向蛋白质的反应性酸酐官能团。通过控制疏水性单体甲基丙烯酸月桂酯（LMA）与反应性酸酐官能甲基丙烯酸酯（TMA）和大聚乙二醇甲基丙烯酸酯单体（Mn~950 Da）（O 950）的共聚来实现多官能载体官能度。O 950的RAFT聚合动力学被评价为目标聚合度（DP）、初始链转移剂与引发剂的比率（[CTA]o/[I]o）和溶剂浓度的函数。在[CTA]o/[I]o比为10时，对于25和50的目标DP观察到对聚合的优异控制，如窄且对称的分子量分布和制备嵌段共聚物的能力所证明的。将TMA官能共聚物缀合至肿瘤靶向蛋白转铁蛋白（Tf）。显示靶向共聚物以与多西他赛的商业单瓶制剂（泰索帝）相当的浓度包封多西他赛。在HeLa细胞中进行的体外细胞毒性研究表明，相对于聚合物包封的多西他赛制剂，Tf靶向增强了癌症杀伤特性。
Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a nanoparticulate drug delivery system for chemotherapeutics. The nanoparticles contain a PEG “stealth” corona as well as reactive anhydride functionality designed for conjugating targeting proteins. The multifunctional carrier functionality was achieved by controlling the copolymerization of the hydrophobic monomer lauryl methacrylate (LMA), with a reactive anhydride functional methacrylate (TMA), and a large polyethyleneglycol methacrylate monomer (Mn~950 Da) (O950). RAFT polymerization kinetics of O950 were evaluated as a function of target degrees of polymerization (DP), initial chain transfer agent to initiator ratio ([CTA]o/[I]o), and solvent concentration. Excellent control over the polymerization was observed for target DPs of 25 and 50 at [CTA]o/[I]o ratio of 10 as evidenced by narrow and symmetric molecular weight distributions and the ability to prepare block copolymers. The TMA-functional copolymers were conjugated to the tumor targeting protein transferrin (Tf). The targeted copolymer was shown to encapsulate docetaxel at concentrations comparable to the commercial single vial formulation of docetaxel (Taxotere). In vitro cytotoxicity studies conducted in HeLa cells show that the Tf targeting enhances the cancer killing properties relative to the polymer encapsulated docetaxel formulation.