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

通过自组装的单甲氧基聚乙二醇-聚乳酸乙醇酸嵌段共聚物共递送阿霉素和槲皮素实现协同抗肿瘤和降低心脏毒性作用

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  • Chemistry
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Science Bulletin

Abstract

Quercetin (Que) is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing anti-tumor 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 anti-tumor 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 nanoparticulate chemotherapy-induced toxicity on normal tissues.

摘要

槲皮素是一种天然的多功能生物黄酮素,具有副作用小、增强化疗药抗肿瘤疗效的潜力。但是在生理环境中,它的水溶性差、结构不稳定,限制了其在临床上的广泛应用。本文通过设计一个由两亲性聚合物甲氧基聚乙二醇和聚乙丙交酯构成的生物相容性好的纳米载体,来共递送疏水的槲皮素和亲水的阿霉素。利用体外细胞实验和动物体内肿瘤模型对该药物共递送体系的抗肿瘤和预防癌症效果进行了研究。结果表明,槲皮素-阿霉素纳米化的共递送体系可以保护正常血管内皮细胞免受未纳米化的或纳米化的阿霉素的细胞毒性作用,同时可以增强对癌细胞的杀伤作用。相比于未纳米化的和纳米化的阿霉素,本文设计的这种共递送槲皮素和阿霉素的纳米体系能更好的协同抑制肿瘤的生长,同时将血清中的各项心脏功能指标维持在正常水平。

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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).

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Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China

    Waseem Akhtar Qureshi, Ruifang Zhao, Tianjiao Ji, Yanping Ding, Ayeesha Mujeeb, Guangjun Nie & Yuliang Zhao

  2. Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA

    Hai Wang

  3. National Institute for Biotechnology and Genetic Engineering (NIBGE), P.O. Box 577, Faisalabad, Pakistan

    Ayesha Ihsan

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  1. Waseem Akhtar Qureshi
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Correspondence to Guangjun Nie or Yuliang Zhao.

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Qureshi, W.A., Zhao, R., Wang, H. et al. Co-delivery of doxorubicin and quercetin via mPEG–PLGA copolymer assembly for synergistic anti-tumor efficacy and reducing cardio-toxicity. Sci. Bull. 61, 1689–1698 (2016). https://doi.org/10.1007/s11434-016-1182-z

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  • DOI: https://doi.org/10.1007/s11434-016-1182-z

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