Surface-modulated and thermoresponsive polyphosphoester nanoparticles for enhanced intracellular drug delivery  

作　　者：LI Yang WANG Feng SUN TianMeng DU JinZhi YANG XianZhu WANG Jun 

机构地区：[1]Department of Polymer Science and Engineering, University of Science and Technology of China [2]Hefei National Laboratory for Physical Sciences at Microscale [3]School of Life Sciences, University of Science and Technology of China [4]School of Medical Engineering, Hefei University of Technology [5]High Magnetic Field Laboratory of CAS, University of Science and Technology of China

出　　处：《Science China Chemistry》2014年第4期579-585,共7页中国科学（化学英文版）

基　　金：supported by the Ministry of Science and Technology of China(2010CB934001);the National Natural Science Foundation of China(51125012,51203145)

摘　　要：The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intra- cellular drug delivery. By developing a polymeric nanoparticle composed of poly（aliphatic ester） as the inner core and ther- moresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.

关 键 词：THERMORESPONSIVE drug release POLYPHOSPHOESTER drug resistance 

分 类 号：O634.51[理学—高分子化学]