Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, South Korea.
Int J Pharm. 2012 May 10;427(2):435-42. doi: 10.1016/j.ijpharm.2012.01.034. Epub 2012 Feb 7.
pH-Responsive polymeric micelles have been investigated as drug carriers for chemotherapy. Ligand-mediated polymeric micelles, which can penetrate the target tumors due to their high binding affinity to a specific receptor on the surface of tumors, were developed to achieve targeted drug delivery. In this study, biotin-conjugated methoxypoly(ethylene glycol)-grafted-poly(β-amino ester) was prepared for active and pH-sensitive tumor targeting. These polymers were modified by cholesteryl chloroformate to improve the hydrophobicity of the micelle core. The structure of the biotin-conjugated polymer was confirmed by (1)H NMR spectroscopy, and the existence of biotin at the surface of the polymeric micelles was evaluated by an 4'-hydroxyazobenzene-2-carboxylic acid/avidin (HABA/avidin) binding assay at different pHs. The micelle properties were determined by dynamic light scattering and the result showed that the mean size of the polymeric micelles was approximately 20 nm. For cancer therapy, doxorubicin (DOX) was loaded into the polymeric micelles with a high loading efficiency. From the in vitro cellular uptake results, the biotin-conjugated polymeric micelles can effectively release doxorubicin at acidic tumor cells compared to the micelles without biotin. Overall, biotin-conjugated pH-responsive polymeric micelles have great potential to be used as drug carriers.
pH 响应性聚合物胶束已被研究作为化疗的药物载体。配体介导的聚合物胶束由于其与肿瘤表面特定受体的高结合亲和力，可以穿透靶肿瘤，从而实现靶向药物传递。在这项研究中，制备了生物素缀合的甲氧基聚（乙二醇）接枝聚（β-氨基酯），用于主动和 pH 敏感的肿瘤靶向。这些聚合物通过氯甲酸胆固醇进行修饰，以提高胶束核心的疏水性。通过（1）H NMR 光谱证实了生物素缀合聚合物的结构，并通过在不同 pH 值下的 4'-羟基偶氮苯-2-羧酸/亲和素（HABA/亲和素）结合测定评估了生物素在聚合物胶束表面的存在。通过动态光散射测定了胶束的性质，结果表明聚合物胶束的平均粒径约为 20nm。用于癌症治疗，阿霉素（DOX）以高载药效率载入聚合物胶束中。从体外细胞摄取结果来看，与没有生物素的胶束相比，生物素缀合的 pH 响应性聚合物胶束可以在酸性肿瘤细胞中有效地释放阿霉素。总的来说，生物素缀合的 pH 响应性聚合物胶束具有作为药物载体的巨大潜力。
