title: Bromines on N-allyl position of cationic porphyrins affect both radio- and photosensitizing properties.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Picard
authors.forename: Hasrat
authors.initials: H
authors.lastname: Ali
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
authors.forename: Klaus
authors.initials: K
authors.lastname: Klarskov
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
mesh_terms: 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
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen; D001966:Bromine