Yan Rui, Liu Xinyi, Xiong Junjie, Feng Qiyi, Xu Junhuai, Wang Haibo, Xiao Kai
College of Biomass Science and Engineering, Sichuan University Chengdu 610065 China
National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University Chengdu 610041 China
RSC Adv. 2020 Apr 6;10(23):13889-13899. doi: 10.1039/d0ra01241f. eCollection 2020 Apr 1.
Polymeric micelles have great potential in drug delivery systems because of their multifunctional adjustability, excellent stability, and biocompatibility. To further increase the drug loading efficiency and controlled release ability, a pH-responsive hyperbranched copolymer methoxy poly(ethylene glycol)--polyethyleneimine-poly(ε-Cbz-l-lysine) (MPEG-PEI-PBLL) was synthesized successfully. MPEG-PEI-NH was synthesized to initiate the ring-opening polymerization of benzyloxycarbonyl substituted lysine -carboxyanhydride (-lys NCA). The introduction of Schiff bases in the polymer make it possible to respond to the variation of pH values, which cleaved at pH 5.0 while stable at pH 7.4. As the polymer was amphiphilic, MPEG-PEI-PBLL could self-assemble into micelles. Owing to the introduction of PEI, which make the copolymer hyperbranched, the pH-responsive micelles could efficiently encapsulate theranostic agents, such as doxorubicin (DOX) for chemotherapy and NIRF dye DiD for near-infrared (NIR) imaging. The drug delivery system prolonged the drug circulation time in blood and allowed the drug accumulate effectively at the tumor site. Following the guidance, the DOX was applied in chemotherapy to achieve cancer therapeutic efficiency. All the results demonstrate that the polymer micelles have great potential for cancer theranostics.
聚合物胶束由于其多功能可调性、优异的稳定性和生物相容性，在药物递送系统中具有巨大潜力。为了进一步提高载药效率和控释能力，成功合成了一种pH响应性超支化共聚物甲氧基聚（乙二醇）-聚乙烯亚胺-聚（ε-苄氧羰基-L-赖氨酸）（MPEG-PEI-PBLL）。合成了MPEG-PEI-NH以引发苄氧羰基取代的赖氨酸-N-羧酸酐（-Lys NCA）的开环聚合。聚合物中席夫碱的引入使其能够响应pH值的变化，在pH 5.0时裂解而在pH 7.4时稳定。由于该聚合物具有两亲性，MPEG-PEI-PBLL可以自组装成胶束。由于引入了使共聚物超支化的PEI，pH响应性胶束可以有效地包封治疗诊断剂，如用于化疗的阿霉素（DOX）和用于近红外（NIR）成像的近红外荧光染料DiD。该药物递送系统延长了药物在血液中的循环时间，并使药物有效地在肿瘤部位蓄积。在该指导下，DOX被应用于化疗以实现癌症治疗效果。所有结果表明，聚合物胶束在癌症治疗诊断方面具有巨大潜力。
