Preparation and Biological Characterization of Polymeric Micelle Drug Carriers with Intracellular pH-Triggered Drug Release Property: Tumor Permeability, Controlled Subcellular Drug Distribution, and

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• 作者：Younsoo Bae ; Nobuhiro Nishiyama ; Shigeto Fukushima ; Hiroyuki Koyama ; Matsumura Yasuhiro ; and Kazunori Kataoka
• 刊名：Bioconjugate Chemistry
• 出版年：2005
• 出版时间：January 2005
• 年：2005
• 卷：16
• 期：1
• 页码：122 - 130
• 全文大小：829K
• 年卷期：v.16,no.1(January 2005)
• ISSN：1520-4812

文摘

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. Themicelles were prepared from self-assembling amphiphilic block copolymers, poly(ethylene glycol)-poly(aspartate hydrazone adriamycin), in which the anticancer drug, adriamycin, was conjugated to thehydrophobic segments through acid-sensitive hydrazone linkers. By this polymer design, the micellescan stably preserve drugs under physiological conditions (pH 7.4) and selectively release them bysensing the intracellular pH decrease in endosomes and lysosomes (pH 5-6). In vitro and in vivostudies show that the micelles have the characteristic properties, such as an intracellular pH-triggereddrug release capability, tumor-infiltrating permeability, and effective antitumor activity with extremelylow toxicity. The acquired experimental data clearly elucidate that the optimization of both thefunctional and structural features of polymeric micelles provides a promising formulation not onlyfor the development of intracellular environment-sensitive supramolecular devices for cancertherapeutic applications but also for the future treatment of intractable cancers with limitedvasculature.