Xu Feng, Li Haidong, Yao Qichao, Ge Haoying, Fan Jiangli, Sun Wen, Wang Jingyun, Peng Xiaojun
State Key Laboratory of Fine Chemicals , Dalian University of Technology , 2 Linggong Road , Dalian 116024 , P. R. China . Email:
School of Life Science and Biotechnology , Dalian University of Technology , 2 Linggong Road , Dalian 116024 , P. R. China.
Chem Sci. 2019 Oct 2;10(45):10586-10594. doi: 10.1039/c9sc03355f. eCollection 2019 Dec 7.
Photodynamic therapy is considered as a promising treatment for cancer, but still faces several challenges. The hypoxic environment in solid tumors, imprecise tumor recognition and the lack of selectivity between normal and cancer cells extremely hinder the applications of photodynamic therapy in clinics. Moreover, the "always on" property of photosensitizers also increases the toxicity to normal tissues when exposed to light irradiation. In this study, a hypoxia-activated NIR photosensitizer was synthesized and successfully applied for cancer treatment. is in the inactivated state with low fluorescence whereas its NIR emission ( = 716 nm) was induced reduction caused by nitroreductase at the tumor site. In addition, the reduced product was specially located in the mitochondria and demonstrated a high singlet oxygen production under 660 nm light irradiation, which efficiently induced cell apoptosis (IC = 0.63 μM). The studies carried out in Balb/c mice indicated that was suitable for precise tumor hypoxia imaging and can work as an efficient photosensitizer for restraining tumor growth through the PDT process.
光动力疗法被认为是一种有前景的癌症治疗方法，但仍面临若干挑战。实体瘤中的缺氧环境、不精确的肿瘤识别以及正常细胞与癌细胞之间缺乏选择性极大地阻碍了光动力疗法在临床上的应用。此外，光敏剂的“常开”特性在暴露于光照时也会增加对正常组织的毒性。在本研究中，合成了一种缺氧激活的近红外光敏剂，并成功应用于癌症治疗。该光敏剂处于低荧光的失活状态，而其近红外发射（λ = 716 nm）是由肿瘤部位的硝基还原酶诱导的还原作用所引发。此外，还原产物特异性定位于线粒体，并在660 nm光照下表现出高单线态氧产生，从而有效诱导细胞凋亡（IC = 0.63 μM）。在Balb/c小鼠中进行的研究表明，该光敏剂适用于精确的肿瘤缺氧成像，并可作为一种有效的光敏剂，通过光动力疗法过程抑制肿瘤生长。
