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Acid/light dual-responsive biodegradable polymeric nanocarriers for efficient intracellular drug delivery

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Abstract

A novel amphiphilic acid/light dual-cleavable diblock copolymer poly(ε-caprolactone)-acetal-nitrobenzyl ester-poly(ethylene glycol) (PCL-PEG) was prepared via the ring-opening polymerization of ε-caprolactone using 5-propargylether-2-nitrobenzyl alcohol as the initiator and subsequent “click” coupling reaction with azide-terminated poly(ethylene glycol) containing acetal group. Both light-cleavable o-nitrobenzyl methyl ester (ONB) and acid-labile acetal were used as the linkages in between the hydrophilic and hydrophobic polymer blocks. In aqueous solution, the copolymer self-assembled into the spherical polymeric nanoparticles, which were stable under physiological conditions and retained the anticancer drug doxorubicin (DOX) inside. Triggered by acid or UV irradiation, the DOX release rate was significantly enhanced, due to the correspondent degradation of acetal or ONB linkages under the stimulus. In addition, confocal laser scanning microscopy studies further demonstrated the DOX-loaded nanodrug could be efficiently taken up by HeLa cells and exhibited the enhanced DOX release into the cytoplasm upon UV irradiation. Furthermore, in vitro cytotoxicity study verified UV irradiation could improve the antitumor efficacy of the nanodrug against HeLa cells. Thus, this work provides a new method of the design of dual-responsive biodegradable polymers for drug delivery.

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Acknowledgements

This work was financially supported by the Natural Science Foundation of Jiangsu Province, China (BK20171263), China Postdoctoral Science Foundation (2018M630548), Postgraduate Research & Practice Innovation Program of Jiangsu Province, China (KYCX18_2603) and the Lianyungang Industry Prospect and Common Key Technologies Program (No. CG1602).

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  1. Jiangsu Key Laboratory of Function Control Technology for Advanced Materials, School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang, 222005, People’s Republic of China

    Yuanyuan Zhang, Xiang Cao, Tian Liang & Zhiwei Tong

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  1. Yuanyuan Zhang
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Correspondence to Yuanyuan Zhang.

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Zhang, Y., Cao, X., Liang, T. et al. Acid/light dual-responsive biodegradable polymeric nanocarriers for efficient intracellular drug delivery. Polym. Bull. 76, 1775–1792 (2019). https://doi.org/10.1007/s00289-018-2470-3

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