Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123, China.
Nanoscale. 2013 Oct 7;5(19):8925-9. doi: 10.1039/c3nr03262k. Epub 2013 Aug 9.
Polymeric micelles (∼10 nm) have been prepared from the amphiphilic oligomer comprising oligomeric polystyrene as the hydrophobic inner core and half of EDTA (-N(CH₂COOH)₂) as the hydrophilic outermost shell. After chelating cisplatin with -N(CH₂COOH)₂ in water, polymeric micelles containing Pt on the spherical surface have been easily obtained. Since the chelate group is introduced into the amphiphilic oligomer as the terminal group by a RAFT agent, the chelation of cisplatin with PS(COOH)₂ is almost stoichiometric. The drug carrier based on PS(COOH)₂ showed a high loading efficiency (>70%) towards cisplatin. The release of the therapeutic Pt from the cisplatin-loaded composites (PS(COOH)₂-Pt) triggered under weak acidic conditions resulted in good Pt-release and accumulation in tumor cells. Both in vitro and in vivo, the chelated cisplatin inhibited Sk-Br3 cancer more effectively than the intact cisplatin does. Furthermore, neither PS(COOH)₂ nor PS(COOH)₂-Pt showed obvious systematic toxicity.
聚合物胶束（约 10nm）由两亲性低聚物制备得到，该低聚物的疏水性内核为齐聚聚苯乙烯，亲水性最外层为 EDTA（-N(CH₂COOH)₂）的一半。在水中用 -N(CH₂COOH)₂与顺铂螯合后，很容易得到在球形表面上含有 Pt 的聚合物胶束。由于螯合基团通过 RAFT 试剂作为末端基团引入两亲性低聚物中，因此 PS(COOH)₂与顺铂的螯合几乎是化学计量的。基于 PS(COOH)₂的药物载体对顺铂的载药效率很高（>70%）。在弱酸性条件下引发载顺铂的复合材料（PS(COOH)₂-Pt）中治疗性 Pt 的释放导致良好的 Pt 释放和在肿瘤细胞中的积累。无论是在体外还是体内，与完整的顺铂相比，螯合顺铂对 Sk-Br3 癌症的抑制作用更为有效。此外，PS(COOH)₂和 PS(COOH)₂-Pt 均没有明显的系统毒性。
