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H2O2-Activated Oxidative Stress Amplifier Capable of GSH Scavenging for Enhancing Tumor Photodynamic Therapy

Abstract

Photodynamic therapy (PDT), as a clinically approved cancer treatment approach, relied on the generation of excess reactive oxygen species (ROS) to eradicate tumor cells by inducing the oxidative stress. Unfortunately, the tumor endogenous glutathione (GSH) is overexpressed, which would eliminate the ROS and restrict the therapeutic efficacy of PDT. Herein, we reported a H2O2-activated oxidative stress amplifier (OSA) to enhance the ROS generation for PDT via GSH scavenging. Cinnamaldehyde (Cin) and chlorin e6 (Ce6) were applied as the GSH scavenger and photosensitizer separately, which were assembly with ROS responsive amphipathic polymer (DPL) to form DPL@CC micelles as the OSA. In the blood circulation, the OSA could effectively protect the Cin from albumin binding to retain its GSH depletion ability. Once the OSA reached tumor site, the high level of H2O2 triggered the degradation of DPL and lead to the release of Cin and Ce6. Subsequently, the released Cin could react with the intracellular GSH by Michael Addition and downregulate the GSH level to about 18.9% versus untreated cells for weakening the anti-oxidation ability of tumor cells. Thus, it provided preferable environment for PDT to obtain oxidative stress amplifying effect and superior anti-cancer efficacy of 94% growth inhibition. The preparation of H2O2 activated oxidative stress amplifier was a convincing strategy for promoting the intracellular ROS generation and enhancing the tumor PDT efficacy, which could also polish up the clinical application of PDT.

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Publication details

The article was received on 24 Aug 2019, accepted on 24 Sep 2019 and first published on 02 Oct 2019


Article type: Paper
DOI: 10.1039/C9BM01354G
Biomater. Sci., 2019, Accepted Manuscript

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    H2O2-Activated Oxidative Stress Amplifier Capable of GSH Scavenging for Enhancing Tumor Photodynamic Therapy

    Y. Liu, Z. Zhou, Y. Liu, Y. Li, X. Huang, C. Qian and M. Sun, Biomater. Sci., 2019, Accepted Manuscript , DOI: 10.1039/C9BM01354G

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