The photodynamic activities of dimethyl 131-[2-(guanidinyl)ethylamino] chlorin e6 photosensitizers in A549 tumor
- Eur J Med Chem. 2019 Sep 1:177:144-152. doi: 10.1016/j.ejmech.2019.05.050.
- 1. Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China.
- 2. Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000, Croatia.
- 3. Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000, Croatia. Electronic address: [email protected].
- 4. Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China. Electronic address: [email protected].
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.