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
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, PR China.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, PR China; Shenzhen Research Institute, Dalian University of Technology, Nanshan District, Shenzhen, 518057, PR China.
Biomaterials. 2020 Sep;253:120089. doi: 10.1016/j.biomaterials.2020.120089. Epub 2020 May 3.
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 (λ = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.
近年来，光动力疗法已发展成为一种有前景的癌症治疗方法。然而，传统的光敏剂对肿瘤缺乏识别能力和特异性，这会对正常组织造成严重的副作用，而酶激活的光敏剂由于对肿瘤具有高选择性，能够解决这些难题。氨肽酶N（APN，氨肽酶N/CD13）作为一种肿瘤标志物，因其在各种肿瘤的细胞膜表面高度表达，已成为一种关键的靶向物质，这已成为抗肿瘤药物和荧光探针研究的一个关键点。基于此，本文首次开发了一种用于肿瘤成像和光动力治疗的APN激活的近红外（NIR）光敏剂（APN-CyI），并在体外和体内成功应用。研究表明，APN-CyI可被肿瘤细胞中的APN激活，水解为荧光性的CyI-OH，其特异性定位于癌细胞的线粒体中，并在近红外照射下表现出高单线态氧产率，且能有效诱导癌细胞凋亡。引人注目的是，对Balb/c小鼠的体内实验表明，APN-CyI能够对肿瘤内源性APN实现近红外荧光成像（λ = 717 nm），并在近红外照射下具有有效的肿瘤抑制作用。
