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Synergistic chemo–photodynamic therapy mediated by light-activated ROS-degradable nanocarriers

Abstract

Combination of chemotherapy and photodynamic therapy (PDT) using polymeric nanocarriers is effective to improve therapeutic efficiency against cancer. Yet, in most reported cases, due to the lack of synergistic mechanisms, chemotherapy and PDT work independently rather than synergistically―functions of chemotherapeutic drugs and photosensitizers in nanocarriers were independent when they were delivered to cancer cells. Here, we demonstrate the construction of reactive oxygen species (ROS)-degradable nanoparticles (NPs) based on phenylboronic pinacol ester-conjugated dextran (PPE–Dex) through a membrane-extrusion emulsification approach for co-delivery of anticancer drug (e.g., doxorubicin, Dox) and photosensitizer (e.g., chlorin e6, Ce6). When exposed to the 655-nm laser irradiation, ROS that generated by encapsulated Ce6 not only induced significant PDT effect in cancer cells, but also triggered rapid oxidization and degradation of PPE–Dex, resulting in quick release and enhanced intra-nuclei accumulation of Dox. In vitro cytotoxicity and combination index (CI) assay indicated that PPE–Dex NPs offered remarkable synergistic therapeutic effects of Dox and Ce6 against cancer cells under irradiation. Furthermore, the drug release profiles can be well regulated by changing the irradiation time to satisfy different demands in various treatment programs. Our results demonstrated that such ROS-degradable polymeric NPs with light-activated disassembly capability are promising carriers for synergistic photodynamic-chemo therapy in cancer therapy.

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Publication details

The article was received on 16 Nov 2018, accepted on 03 Dec 2018 and first published on 04 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB03030H
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Synergistic chemo–photodynamic therapy mediated by light-activated ROS-degradable nanocarriers

    Y. Chen, Y. Gao, Y. Li, K. Wang and J. Zhu, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB03030H

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