Bromines on N-allyl position of cationic porphyrins affect both radio- and photosensitizing properties.
With the aim to develop improved dual-action sensitizers suitable for both photodynamic therapy (PDT) and radiotherapy, we prepared a series of metal and metal-free cationic porphyrins, brominated either on beta- or N-allyl positions. Photo- and radiosensitizing efficacy was evaluated in MDA-MB-231 breast cancer cells incubated with 1 muM porphyrin and treated with graded doses of visible light or 0-6 Gy of 60Co gamma irradiation. Metabolic activity after PDT or cell survival after gamma irradiation were estimated by a colorimetric (MTT) or clonogenicity assay, respectively. The highest photo- and radiosensitizing activities were observed with the porphyrins substituted with bromines on N-allyl positions. The non-metalated N-allyl bromoporphyrin exhibited the highest photocytotoxicity (LD50=4.1+/-0.6 J cm(-2), compared to 15.3+/-2.2 J cm(-2) for the non-brominated analog). The radiosensitizing capacity of the cationic porphyrins was also affected by these substitutions with the non-metalated N-allyl bromo analog showing the best improvement (LD50=1.2+/-0.4 Gy vs. 3.6+/-0.9 Gy for the non-brominated analog). The increased photodynamic and radiosensitizing potencies due to bromine addition hold potential for the development of new, improved drugs for cancer treatment in combination with photodynamic and radiation therapy.
Picard
Nathalie
N
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Québec, Canada J1H 5N4.
Ali
Hasrat
H
van Lier
Johan E
JE
Klarskov
Klaus
K
Paquette
Benoit
B
D001966:Bromine / Q000737:chemistry*; D008027:Light; D008958:Models, Molecular; D017319:Photosensitizing Agents / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry* / Q000528:radiation effects; D011846:Radio Waves; D026082:Singlet Oxygen / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen; D001966:Bromine