Center for Education and Research on Macromolecules, University of Liege, B6 Sart-Tilman, B-4000 Liege, Belgium.
Acta Biomater. 2011 Oct;7(10):3700-7. doi: 10.1016/j.actbio.2011.06.014. Epub 2011 Jun 17.
Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(ε-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment.
评价 pH 触发靶向胶束的生物相容性，研究聚（环氧乙烷）（PEO）涂层对胶束隐形特性的影响。在酸性条件下质子化时，pH 敏感的聚（2-乙烯基吡啶）（P2VP）链段伸展，在胶束的外围呈现正电荷，同时也是一种靶向单元模型。聚合物胶束基于两种不同的大分子结构，即 ABC 型星型三嵌段共聚物和 ABC 型线性三嵌段共聚物，结合了三种不同的聚合物链段，即疏水性聚（ε-己内酯）、PEO 和 P2VP。在生理 pH 值下形成中性聚合物胶束。这些系统被测试其避免巨噬细胞摄取的能力、补体激活以及在小鼠体内系统注射后的药理行为，这取决于它们的构象（中性或质子化）。质子化后，补体激活和巨噬细胞摄取比中性系统高两倍。相比之下，当 P2VP 链段和靶向单元在生理 pH 值下被 PEO 壳包裹时，胶束隐形特性得到改善，允许它们在体内系统注射，预计在血液中有较长的循环时间。因此，开发了对 pH 响应的智能系统，为靶向递送到酸性肿瘤环境提供了很大的希望。
