A complex of cyclohexane-1,2-diaminoplatinum with an amphiphilic biodegradable polymer with pendant carboxyl groups.
A complex of cyclohexane-1,2-diaminoplatinum with an amphiphilic biodegradable polymer with pendant carboxyl groups.
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DOI：
10.1016/j.actbio.2012.01.007
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发表时间：
2012-05
影响因子：
9.7
通讯作者：
Haihua Xiao;Dongfang Zhou;Shi Liu;Yonghui Zheng;Yubin Huang;X. Jing
中科院分区：
文献类型：
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作者：
Haihua Xiao;Dongfang Zhou;Shi Liu;Yonghui Zheng;Yubin Huang;X. Jing
选择含有悬垂羧基的可生物降解两亲共聚物MPEG-b-P（LA-co-MCC）作为奥沙利铂活性抗癌部分（DACH-Pt）的药物载体，形成MPEG-b-P（LA-co-MCC/Pt）配合物。它能够自组装成平均直径为30-40nm的胶束，表面电位接近-10mV。典型铂含量为10wt.%。胶束表现出酸反应性药物释放动力学，这有利于药物在细胞内环境中的释放。通过高效液相色谱、电感耦合等离子体质谱和x射线光电子能谱分析，发现Pt（II）主要以dach -Pt- cl2和DACH-Pt2+-(H2O)2的形式在150mM NaCl溶液和纯水中释放。体外评价表明，与奥沙利铂相比，胶束对SKOV-3、HeLa和EC-109癌细胞具有相同或更高的细胞毒性。对SKOV-3细胞的细胞毒性增强归因于细胞通过内吞作用将胶束有效内化以及SKOV-3细胞对铂类药物的敏感性。这种新型的可生物降解的两亲性共聚物铂类药物具有很大的临床应用潜力。
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 30–40nm, and a surface potential near -10mV. The typical platinum content was 10wt.%. 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-Cl2in 150mM NaCl solution and DACH-Pt2+-(H2O)2in 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.