Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy
Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy
复制标题
DOI：
10.1021/bc0498166
复制
发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Bae, Y;Nishiyama, N;Kataoka, K
本研究开发了一种新型的细胞内pH敏感的聚合物胶束药物载体，它可以控制药理活性药物的系统、局部和亚细胞分布。胶束是由自组装的两亲嵌段共聚物聚乙二醇-聚天冬氨酸肼-阿霉素制得的，其中抗癌药物阿霉素通过酸敏肼连接物连接到疏水链段上。通过这种聚合物设计，胶束可以在生理条件下(pH 7.4)稳定地保存药物，并通过感知内切体和溶酶体(pH 5-6)细胞内pH的下降来选择性地释放药物。体外和体内研究表明，该胶束具有细胞内pH触发的药物释放能力、肿瘤的渗透性和极低毒性的有效抗肿瘤活性等特性。所获得的实验数据清楚地表明，聚合物胶束的功能和结构特征的优化不仅为开发用于癌症治疗的细胞内环境敏感超分子装置提供了一个有前途的配方，也为未来治疗血管有限的难治性癌症提供了一个很有前途的方案。
A novel intracellular pH-sensitive polymeric micelle drug carrier that controls the systemic, local, and subcellular distributions of pharmacologically active drugs has been developed in this study. The micelles were prepared from self-assembling amphiphilic block copolymers, poly(ethylene glycol)-poly(aspartate hydrazone adriamycin), in which the anticancer drug, adriamycin, was conjugated to the hydrophobic segments through acid-sensitive hydrazone linkers. By this polymer design, the micelles can stably preserve drugs under physiological conditions (pH 7.4) and selectively release them by sensing the intracellular pH decrease in endosomes and lysosomes (pH 5-6). In vitro and in vivo studies show that the micelles have the characteristic properties, such as an intracellular pH-triggered drug release capability, tumor-infiltrating permeability, and effective antitumor activity with extremely low toxicity. The acquired experimental data clearly elucidate that the optimization of both the functional and structural features of polymeric micelles provides a promising formulation not only for the development of intracellular environment-sensitive supramolecular devices for cancer therapeutic applications but also for the future treatment of intractable cancers with limited vasculature.