State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People's Republic of China.
Acta Biomater. 2012 May;8(5):1859-68. doi: 10.1016/j.actbio.2012.01.007. Epub 2012 Jan 11.
A biodegradable and amphiphilic copolymer, MPEG-b-P(LA-co-MCC), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (DACH-Pt) of oxaliplatin to form an MPEG-b-P(LA-co-MCC/Pt) complex. It was able to self-assemble into micelles with a mean diameter of 30-40 nm, and a surface potential near -10 mV. The typical platinum content was 10 wt.%. The micelles showed acid-responsive drug release kinetics, which is beneficial for drug release in the intracellular environment. The Pt(II) species were released mainly in the form of DACH-Pt-Cl(2) in 150 mM NaCl solution and DACH-Pt(2+)-(H(2)O)(2) in pure water according to the results obtained by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. In vitro evaluation showed that the micelles displayed the same or higher cytotoxicities against SKOV-3, HeLa, and EC-109 cancer cells compared with oxaliplatin. The enhanced cytotoxicity against SKOV-3 cells is attributed to effective internalization of the micelles by the cells via endocytosis and the sensitivity of SKOV-3 cells to platinum drugs. This novel biodegradable and amphiphilic copolymer-based platinum drug will have great potential application in clinical use.
一种可生物降解的两亲性共聚物 MPEG-b-P(LA-co-MCC)，其中含有侧挂羧基，被选择为奥沙利铂的活性抗癌部分（DACH-Pt）的药物载体，以形成 MPEG-b-P(LA-co-MCC/Pt) 复合物。它能够自组装成平均直径为 30-40nm 的胶束，表面电位接近-10mV。典型的铂含量为 10wt%。胶束显示出酸响应的药物释放动力学，这有利于在细胞内环境中释放药物。根据高效液相色谱与电感耦合等离子体质谱和 X 射线光电子能谱联用的结果，Pt(II)物种主要以 DACH-Pt-Cl(2)的形式在 150mM NaCl 溶液中释放，以 DACH-Pt(2+)-(H(2)O)(2)的形式在纯水中释放。体外评价表明，与奥沙利铂相比，胶束对 SKOV-3、HeLa 和 EC-109 癌细胞表现出相同或更高的细胞毒性。对 SKOV-3 细胞的增强的细胞毒性归因于胶束通过内吞作用被细胞有效内化，以及 SKOV-3 细胞对铂类药物的敏感性。这种新型的基于可生物降解的两亲性共聚物的铂类药物在临床应用中具有巨大的潜力。
