期刊
BIOMATERIALS
卷 185, 期 -, 页码 301-309出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.09.033
关键词
Hypoxia activated prodrug; Photodynamic therapy; Liposomes; Tumor hypoxia; Drug delivery
资金
- Special Foundation for State Major Research Program of China [2016YFC0106602, 2016YFC0106601]
- National Natural Science Foundation of China [21645005, 21475008]
Hypoxia tumor microenvironment is a major challenge for photodynamical therapy (PDT), and hypoxia-activated chemotherapy combined PDT could be promising for enhanced anticancer therapy. In this study, we report an innovative 2-nitroimidazole derivative conjugated polyethylene glycol (PEG) amphoteric polymer theranostic liposome encapsulated a photosensitizer Chlorin e6 (Ce6), hypoxia-activated prodrug Tirapazamine (TPZ) and gene probe for synergistic photodynamic-chemotherapy. Ce6-mediated PDT upon irradiation with a laser induces hypoxia, which leads to the disassembly of the liposome and activates the antitumor activity of TPZ for improved cancer cell-killing. The released co-delivered gene probe could effectively detect the oncogenic intracellular biomarker for diagnosis. Both in vitro and in vivo studies demonstrated the greatly improved anticancer activity compared to conventional PDT. This work contributes to the design of hypoxia-responsive multifunctional liposome for tumor diagnosis and hypoxia-activated chemotherapy combined PDT for synergetic therapy, which holds great promise for future cancer therapy.
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