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Light-triggered theranostic liposomes for tumor diagnosis and combined photodynamic and hypoxia-activated prodrug therapy

Author:
Zhang, Kai, Zhang, Yuedong, Meng, Xiangdan, Lu, Huiting, Chang, Huan, Dong, Haifeng, Zhang, Xueji
Source:
Biomaterials 2018 v.185 pp. 301-309
ISSN:
0142-9612
Subject:
antineoplastic activity, biomarkers, chlorins, drug therapy, genes, hypoxia, in vivo studies, irradiation, neoplasms, photosensitizing agents, polyethylene glycol
Abstract:
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 anti-cancer 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.
Agid:
6154545