Co-delivery of doxorubicin and quercetin via mPEG-PLGA copolymer assembly for synergistic anti-tumor efficacy and reducing cardio-toxicity  

作　　者：Waseem Akhtar Qureshi Ruifang Zhao Hai Wang Tianjiao Ji Yanping Ding Ayesha Ihsan Ayeesha Mujeeb Guangjun Nie Yuliang Zhao 

机构地区：[1]CAS Key Laboratory for Biomedical Effects of Nanomaterialsand Nanosafety, Center for Excellence in Nanoscience, NationalCenter for Nanoscience and Technology, Beijing 100190, China [2]Department of Biomedical Engineering, The Ohio StateUniversity, Columbus, OH 43210, USA [3]National Institute for Biotechnology and Genetic Engineering(NIBGE), P.O. Box 577, Faisalabad, Pakistan

出　　处：《Science Bulletin》2016年第21期1689-1698,共10页科学通报（英文版）

基　　金：Acknowledgments This work was supported by the National Basic Research Program of China （2012CB934004）, the National Funds for Distinguished Young Scientists （31325010）, the Key Research Program of the Chinese Academy of Sciences （KGZD-EW-T06） and the National Natural Science Foundation of China （31300822）.

摘　　要：Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.橡黄素(Que ) 是自然多功能的 bioflavonoid，并且为减少不利副作用并且提高化学疗法的药的反肿瘤功效显示出大潜力。然而，它的临床的申请在生理的系统由于很低的溶解度和结构的不稳定性被限制。此处，我们共同交付由开发 amphiphilic 聚合物包括的 biocompatible nanocarrier 的恐水病的橡黄素和吸水的 doxorubicin (纪录影片) ， methoxy poly (乙烯乙二醇) 并且 poly (D， L-lactide-co-glycolide ) 分别地。反肿瘤和这个系统的预防功效被评估在细胞并且动物模型。我们说明的调查结果 Dox-Que nanoparticulate 明确的表达保护了正常脉管的 endothelial 房间免受免费的任何一个或 nanoparticulate 的伤害导致 doxorubicin 的 cytotoxicity 和增加的癌症房间死亡。与免费 doxorubicin 和它的 nanoformulation 相比，用我们的 nanosystem 的橡黄素和 doxorubicin 的合作交货 synergistically 禁止了肿瘤生长，当在浆液维持心脏的功能指示物的正常层次并且在心织物恢复组织病理学说的损坏时。这研究为提高反癌症药功效并且减少 nanoparticulate 表明有希望的策略正常纸巾上的导致化疗的毒性。

关 键 词：Polymeric nanoparticles . Doxorubicin Quercetin - Cardio-toxicity - Cancer therapy 

分 类 号：N[自然科学总论]