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Redox-responsive PEGylated self-assembled prodrug-nanoparticles formed by single disulfide bond bridge periplocymarin-vitamin E conjugate for liver cancer chemotherapy

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posted on 2017-08-24, 08:12 authored by Huiyun Zhang, Wenqian Xu, Emmanuel Omari-Siaw, Yingkun Liu, Baoding Chen, Deyu Chen, Jiangnan Yu, Ximing Xu

Periplocymarin (PPM), a cardiac glycoside, has a narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity which hinder its wide clinical applications in cancer treatment. Herein, we report novel redox-responsive prodrug-nanoparticles (MPSSV-NPs) self-assembled by co-nanoprecipitation of PPM-vitamin E conjugate and a PEG derivative of linoleate (mPEG2000-LA) in water. It was found that the characteristics of PPM-vitamin E nanoparticles (PSSV-NPs) were improved through co-nanoprecipitation with increased percentages of mPEG2000-LA. Moreover, the MPSSV-NPs were optimized according to the in vitro release and cytotoxicity study. Furthermore, the optimized MPSSV-NPs dramatically enhanced the circulation time and tumor distribution of PSSV-NPs after single intravenous injection. The in vivo studies in malignant H22-bearing mice revealed that MPSSV-NPs could effectively suppress tumor growth without causing obvious systemic toxicity. Altogether, these results suggested that MPSSV-NPs could offer a safe, multifunctional and viable nanoplatform for cardiac glycosides in cancer treatment.

Funding

National Natural Science Foundation of China10.13039/501100001809

the National Natural Science Foundation of China10.13039/50110000180981373371This work was supported by the National Natural Science Foundation of China (30973677, 81373371), Program for Scientific Research Innovation Team in Colleges and Universities of Jiangsu Province and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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