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

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 capab...

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Veröffentlicht in:Biomaterials 2020-09, Vol.253, p.120089-120089, Article 120089
Hauptverfasser: Zhou, Xiao, Li, Haidong, Shi, Chao, Xu, Feng, Zhang, Zhen, Yao, Qichao, Ma, He, Sun, Wen, Shao, Kun, Du, Jianjun, Long, Saran, Fan, Jiangli, Wang, Jingyun, Peng, Xiaojun
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Sprache:eng
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Zusammenfassung: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 (λem = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2020.120089