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Selective Cancer Treatment via Cascaded Photodynamic Sensitization of Hypoxia-Responsive Drug Delivery

Abstract

The precise and selective delivery of chemodrugs into tumors represents a critical requirement for anti-cancer therapy. Intelligent delivery systems that are responsive to a single internal or external stimulus often lack sufficient cancer selectivity, which compromises the drug efficacy and induces undesired side effects. To overcome this dilemma, we herein report a cancer-targeting vehicle which allows highly cancer-selective drug release in response to cascaded external (light) and internal (hypoxia) dual triggers. Particularly, doxorubicin (DOX)-loaded, hypoxia-dissociable nanoparticles (NPs) were prepared from self-assembled polyethyleneimine-nitroimidazole (PEI-NI) micelles that were further co-assembled with hyaluronic acid-Ce6 (HC). Upon accumulation in tumor cells, tumor site-specific light irradiation (660 nm, 10 mW/cm2) generated high levels of reactive oxygen species (ROS) and greatly enhanced the hypoxic levels to induce NP dissociation and accordingly DOX release. Synergistic anti-cancer efficacy between DOX-mediated chemotherapy and Ce6-mediated photodynamic therapy (PDT) was thus achieved, resulting in reduced side effects to normal tissues/cells. This study therefore provides an effective tool to control the cancer-specific drug delivery by responding to cascaded multiple triggers, and it renders promising utilities for the programmed combination of chemotherapy and PDT toward cancer treatment.

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Publication details

The article was received on 15 Oct 2017, accepted on 25 Dec 2017 and first published on 27 Dec 2017


Article type: Paper
DOI: 10.1039/C7NR07677K
Citation: Nanoscale, 2017, Accepted Manuscript
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    Selective Cancer Treatment via Cascaded Photodynamic Sensitization of Hypoxia-Responsive Drug Delivery

    H. He, R. Zhu, W. Sun, K. Cai, Y. Chen and L. Yin, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR07677K

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