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H2O2-responsive nano-prodrug for podophyllotoxin delivery

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Abstract

The tumor microenvironment is different from that of normal tissue; therefore, the development of a prodrug that retains its efficacy in the tumor microenvironment can be useful in enhancing the anticancer properties of podophyllotoxin. An innovative podophyllotoxin prodrug (POD-PEG) was designed by linking podophyllotoxin to poly(ethylene glycol)(n) monomethacrylate with a H2O2-responsive oxalate ester bond. POD-PEG can self-assemble into stable nanoparticles (POD-PEG NPs). In vitro experiments demonstrated that the POD-PEG NPs can be activated by hydrogen peroxide resulting in podophyllotoxin release and are highly toxic against colon carcinoma CT26 cells. In vivo biodistribution studies demonstrate that PEGylated POD-PEG NPs are capable of prolonging blood circulation. Intravenous injection of POD-PEG NPs into CT26 tumor-bearing Balb/c mice resulted in a significantly enhanced therapeutic efficacy against tumors, with no significant systemic toxicity. Therefore, this H2O2-responsive prodrug delivery system exhibits good biosafety and provides a novel strategy for the development of drug delivery systems.

Graphical abstract: H2O2-responsive nano-prodrug for podophyllotoxin delivery

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Publication details

The article was received on 04 Mar 2019, accepted on 29 Mar 2019 and first published on 01 Apr 2019


Article type: Paper
DOI: 10.1039/C9BM00344D
Citation: Biomater. Sci., 2019, Advance Article

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    H2O2-responsive nano-prodrug for podophyllotoxin delivery

    K. Ou, Y. Kang, L. Chen, X. Zhang, X. Chen, Y. Zheng, J. Wu and S. Guan, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM00344D

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