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

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.
Ying-Hua Gao 1,  Vanda Lovreković 2,  Akmaral Kussayeva 2,  Dan-Ye Chen 1,  Davor Margetić 3,  Zhi-Long Chen 4
Affiliations

Affiliations

  • 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: margetid@irb.hr.
  • 4 Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China. Electronic address: zlchen1967@qq.com.
PMID: 31132530 DOI: 10.1016/j.ejmech.2019.05.050
Abstract

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.

Keywords

Chlorin e(6) derivative; Guanidine; Photodynamic therapy; Photosensitizers; Reactive oxygen species; Tumor.

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