title: In vitro demonstration of apoptosis mediated photodynamic activity and NIR nucleus imaging through a novel porphyrin.
abstract: We synthesized a novel water-soluble porphyrin THPP and its metalated derivative Zn-THPP having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S. Food and Drug Administration approved and clinically used sensitizer Photofrin, THPP showed ca. 2-3-fold higher in vitro photodynamic activity in different cell lines under identical conditions. The mechanism of the biological activity of these porphyrin systems has been evaluated through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, comet assay, poly(ADP-ribose)polymerase (PARP) cleavage, CM-H(2)DCFDA assay, DNA fragmentation, flow cytometric analysis, fluorescence, and confocal microscopy, which confirm the apoptotic cell death through predominantly reactive oxygen species (ROS). Moreover, THPP showed rapid cellular uptake and are localized in the nucleus of the cells as compared to Hoechst dye and Photofrin, thereby demonstrating its use as an efficient sensitizer in photodynamic therapy and live cell NIR nucleus imaging applications.
authors.forename: Suneesh C
authors.initials: SC
authors.lastname: Karunakaran
authors.forename: P S Saneesh
authors.initials: PS
authors.lastname: Babu
authors.forename: Bollapalli
authors.initials: B
authors.lastname: Madhuri
authors.forename: Betsy
authors.initials: B
authors.lastname: Marydasan
authors.forename: Albish K
authors.initials: AK
authors.lastname: Paul
authors.forename: Asha S
authors.initials: AS
authors.lastname: Nair
authors.forename: K Sridhar
authors.initials: KS
authors.lastname: Rao
authors.forename: Alagar
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Tavarekere K
authors.initials: TK
authors.lastname: Chandrashekar
authors.forename: Ch Mohan
authors.initials: ChM
authors.lastname: Rao
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Pillai
authors.forename: Danaboyina
authors.initials: D
authors.lastname: Ramaiah
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D011166:Porphyrins; D015032:Zinc