Naslov
The photodynamic activities of dimethyl 131-[2- (guanidinyl)ethylamino] chlorin e6 photosensitizers in A549 tumor

Autori
Gao, Ying-Hua ; Lovreković, Vanda ; Kussayeva, Akmaral ; Chen, Dan-Ye ; Margetić, Davor ; Chen, Zhi-Long

Izvornik
European journal of medicinal chemistry (0223-5234) 177 (2019); 144-152

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Chlorin e6 derivative ; Guanidine ; Photodynamic therapy ; Photosensitizers ; Reactive oxygen species ; Tumor

Sažetak
Effective photosensitizers are particularly important factor in clinical photodynamic therapy (PDT). However, there is a scarcity of photosensitizers for simultaneous cancer photo- diagnosis and targeted PDT. Herein, two novel dimethyl 2-(guanidinyl)ethylamino chlorin e6 photosensitizers were synthesized and their efficacy in PDT in A549 tumor was investigated. It was shown that compounds 3 and 4 have a long absorption wavelength in the near infrared region and strong fluorescence emission with slow photo-bleaching rate and markedly strong ability of 1O2 generation. They exhibited lower cytotoxicity and higher photo-cytotoxicity in vitro compared to the known anticancer drug m- THPC in MTT assay in A549 lung cancer cell lines. Compound 4 exhibit better inhibition effect than compound 3 and the IC50 value of compound 4 was 0.197 μM/L under 2 J/cm2 laser irradiation, while compound 3 showed better anti-tumor effects compared to compound 4 in vivo. Intracellular ROS generation was found to be responsible for apoptotic cell death in DCFDA assay. Subcellular localization confirmed the damage site of compounds 3 and 4 in PDT. These findings suggest that the two novel photosensitizers might serve as potential photosensitizers for improved therapeutic efficiency of PDT.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA