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An APN-activated NIR photosensitizer for cancer photodynamic therapy and fluorescence imaging

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Indexed by:Journal Papers

Date of Publication:2021-04-12

Journal:BIOMATERIALS

Volume:253

ISSN No.:0142-9612

Key Words:Aminopeptidase N; Enzyme-activated photosensitizer; PDT; NIR fluorescence imaging

Abstract:Photodynamic therapy has been developed as a prospective cancer treatment in recent years. Nevertheless, conventional photosensitizers suffer from lacking recognition and specificity to tumors, which causing severe side effects to normal tissues, while the enzyme-activated photosensitizers are capable of solving these conundrums due to high selectivity towards tumors. APN (Aminopeptidase N, APN/CD13), a tumor marker, has become a crucial targeting substance owing to its highly expressed on the cell membrane surface in various tumors, which has become a key point in the research of anti-tumor drug and fluorescence probe. Based on it, herein an APN-activated near-infrared (NIR) photosensitizer (APN-CyI) for tumor imaging and photodynamic therapy has been firstly developed and successfully applied in vitro and in vivo. Studies showed that APN-CyI could be activated by APN in tumor cells, hydrolyzed to fluorescent CyI-OH, which specifically located in mitochondria in cancer cells and exhibited a high singlet oxygen yield under NIR irradiation, and efficiently induced cancer cell apoptosis. Dramatically, the in vivo assays on Balb/c mice showed that APN-CyI could achieve NIR fluorescence imaging (lambda(em) = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.

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