Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: Polymeric micelles that are responsive to intracellular pH change
Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: Polymeric micelles that are responsive to intracellular pH change
复制标题
DOI：
10.1002/anie.200250653
复制
发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Bae, Y;Fukushima, S;Kataoka, K
在活体内起作用的生物分子装置的最新发展需要将用于感测体内化学刺激、产生可检测信号和实现适当响应的能力整合到单个分子或分子复合物中。[1]特别地，与细胞内组分或事件（例如离子、蛋白质、酶和pH变化）相互作用的生物制药系统对于实现响应身体特征的编程功能变得重要。[2-6]超分子化学正引起人们的注意，因为它提供了将能够发生结构和动力学变化的不同组分组装成单个分子的方法。[7]在此，我们展示了细胞内定位的pH敏感的超分子组装，改变其结构和荧光激活时，诱导恶性细胞的死亡率。有许多困难，在临床使用的一些生物分子器件，这些问题包括在血液循环中的吞噬清除，全身扩散引起的毒副作用，并排除从细胞膜转运蛋白。一般来说，细胞选择性渗透膜防止未经适当设计的生物分子装置进入。因此，已经提出创建对细胞内环境敏感的生物分子装置作为克服这些生理瓶颈的方法。[8，9]从自组装的酸敏感性两亲嵌段共聚物中，我们制备了一种由细胞内pH值激活的聚合物胶束（图1）。聚合物胶束是一种具有超分子结构的组装体，
The recent development of biomolecular devices that function within the living body has required the integration of capabilities for sensing in vivo chemical stimuli, generating detectable signals, and effecting suitable responses into a single molecule or molecular complex.[1] In particular, biopharmaceutical systems which interact with intracellular components or events such as ions, proteins, enzymes, and pH changes are becoming important for implementing programmed functions that respond to signatures of the body.[2–6] Supramolecular chemistry is attracting attention as it offers methods for assembling different constituents capable of structural and dynamic changes into single molecules.[7] Herein we demonstrate the intracellular localization of a pH-sensitive supramolecular assembly that changes its structure and fluorescences when activated to induce mortality of malignant cells.There are many difficulties in the clinical use of some biomolecular devices, these problems include phagocytic clearance during blood circulation, systemic spread causing toxic side effects, and exclusion from the cell by membrane transporters. In general, the cells selectively permeable membranes prevent the access of biomolecular devices that have not been appropriately designed. Therefore, the creation of biomolecular devices that are sensitive to the intracellular environment has been suggested as a method to overcome these physiological bottlenecks.[8, 9] From self-assembling acid-sensitive amphiphilic block copolymers we have prepared a polymeric micelle that is activated by the intracellular pHvalue (Figure1). The polymeric micelle is a supramolecular assembly with charac-