Center for Education and Research on Macromolecules, University of Liege, B6 Sart-Tilman, B-4000 Liege, Belgium.
Acta Biomater. 2012 Dec;8(12):4215-23. doi: 10.1016/j.actbio.2012.08.049. Epub 2012 Sep 7.
The use of hybrid pH-sensitive micelles based mainly on the (PEO)(129)(P2VP)(43)(PCL)(17) ABC miktoarm star copolymer as potential triggered drug delivery systems was investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine) is considered here in order to impart possible active targeting of the tumor cells. Two architectures were studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer, and the respective hybrid micelles are compared in terms of cytotoxicity (cells viability) and cellular uptake (using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying, on the one hand, the lysosomal integrity after internalization and, on the other hand, the release profile in function of the pH.
主要基于(PEO)(129)(P2VP)(43)(PCL)(17)ABC 型杂臂星型嵌段共聚物的混合 pH 敏感胶束作为潜在的触发药物输送系统进行了研究。在此考虑将该星型共聚物与在 pH 敏感嵌段(聚-2-乙烯基吡啶)上标记有靶向配体(即生物素)的第二种共聚物进行共胶束化,以赋予肿瘤细胞可能的主动靶向性。研究了这两种标记共聚物的两种结构,即杂臂星型或线性 ABC 三嵌段共聚物,并根据细胞毒性(细胞活力)和细胞摄取(使用荧光染料负载的胶束)对相应的混合胶束进行了比较。最后,通过研究内化后溶酶体的完整性以及 pH 依赖性的释放特性,研究了肿瘤细胞细胞溶质中触发的药物释放。
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