Journal
NANOSCALE
Volume 10, Issue 6, Pages 2856-2865Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr07677k
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Funding
- National Natural Science Foundation of China [51573123, 51722305]
- Ministry of Science and Technology of China [2016YFA0201200]
- Natural Science Foundation of Jiangsu Province [BK20161224]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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The precise and selective delivery of chemodrugs into tumors represents a critical requirement for anticancer 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. In particular, doxorubicin (DOX)-loaded, hypoxia-dissociable nanoparticles (NPs) were prepared from self-assembled polyethylenimine-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 cm(-2)) generated high levels of reactive oxygen species (ROS) and greatly enhanced the hypoxic levels to induce NP dissociation and accordingly DOX release. A 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 method to control the cancer-specific drug delivery by responding to cascaded multiple triggers, and it renders promising applications for the programmed combination of chemotherapy and PDT toward cancer treatment.
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