title: Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate.
abstract: Photodynamic therapy (PDT) is a treatment that aims to kill cancer cells by reactive oxygen species, mainly singlet oxygen, produced through light activation of a photosensitiser (PS). Amongst photosensitisers that attracted the most attention in the last decade are cationic and amphiphilic molecules based on porphyrin, chlorin and phthalocyanine structures. Our aim was to join this search for more optimal balance of the lipophilic and hydrophilic moieties in a PS. A new amphiphilic porphyrin, 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (5) was synthesised and characterised by (1)H NMR, UV-vis and fluorescence spectroscopy, and by MALDI-TOF/TOF spectrometry. In vitro photodynamic activity of 5 was evaluated on HeLa cell lines and compared to the activity of the hydrophilic 5-(4-acetamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (7). Low fluence rate (2mWcm(-2)) of red light (643nm) was used for the activation, and both porphyrins showed a drug dose-response as well as a light dose-response relationship, but the amphiphilic porphyrin was presented with significantly lower IC50 values. The obtained IC50 values for 5 were 1.4μM at 15min irradiation time and 0.7μM when the time of irradiation was 30min, while for 7 these values were 37 and 6 times higher, respectively. These results confirm the importance of the lipophilic component in a PS and show a potential for 5 to be used as a PS in PDT applications.
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: nela.malatesti@biotech.uniri.hr.
authors.forename: Nela
authors.initials: N
authors.lastname: Malatesti
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: aharej@uniri.hr.
authors.forename: Anja
authors.initials: A
authors.lastname: Harej
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: sandrakp@biotech.uniri.hr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljević Pavelić
authors.affiliation: Laboratory for Photonics and Quantum Optics, Division of Experimental Physics, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia. Electronic address: mloncaric@irb.hr.
authors.forename: Martin
authors.initials: M
authors.lastname: Lončarić
authors.affiliation: Laboratory of Optics and Optical Thin Films, Division of Materials Physics, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia. Electronic address: Hrvoje.Zorc@irb.hr.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Zorc
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: karlo.wittine@biotech.uniri.hr.
authors.forename: Karlo
authors.initials: K
authors.lastname: Wittine
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: uros.andjelkovic@biotech.uniri.hr.
authors.forename: Uros
authors.initials: U
authors.lastname: Andjelkovic
authors.affiliation: Department of Biotechnology, Centre for high-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia. Electronic address: djosic@biotech.uniri.hr.
authors.forename: Djuro
authors.initials: D
authors.lastname: Josic
mesh_terms: D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006367:HeLa Cells; D006801:Humans; D008027:Light; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D011166:Porphyrins / Q000008:administration & dosage* / Q000138:chemical synthesis*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins
keywords: Amphiphilic structure; Cancer; Cationic porphyrin; Low light dose; Photodynamic therapy