title: Mitochondria-Targeted Photodynamic Therapy with a Galactodendritic Chlorin to Enhance Cell Death in Resistant Bladder Cancer Cells.
abstract: Here, we report the rational design of a new third-generation photosensitizer (PS), a chlorin conjugated with galactodendritic units, ChlGal8, to improve the effectiveness of bladder cancer treatment. ChlGal8shows better photochemical and photophysical properties than a recently reported homologous porphyrin, PorGal8. In addition to inheriting excellent photostability, the ability to generate singlet oxygen, and the ability to interact with the proteins galectin-1 and human serum albumin (HSA), ChlGal8exhibits high absorption in the red region of the electromagnetic spectrum. In vitro studies of anticancer activity of ChlGal8revealed that once this PS is taken up by UM-UC-3 bladder cancer cells, it induces high cytotoxicity after a single dose of light irradiation. In HT-1376 bladder cancer cells resistant to therapy, a second light irradiation treatment enhanced in vitro and in vivo photodynamic efficacy. The enhanced phototoxicity in HT-1376 cancer cells seems to be due to the ability of ChlGal8to accumulate in the mitochondria, via facilitative glucose transporter 1 (GLUT1), in the period between single and repeated irradiation. A photodynamic therapy (PDT) regimen using an extra dose of light irradiation and ChlGal8as PS represents a promising strategy in treating resistant cancers in a clinical setting.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro , 3810-193 Aveiro, Portugal.|IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: Pereira
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro , 3810-193 Aveiro, Portugal.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Silva
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro , 3810-193 Aveiro, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Bispo
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.
authors.forename: Mónica
authors.initials: M
authors.lastname: Zuzarte
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.|Center of Investigation in Environment, Genetics, and Oncobiology , 3001-301 Coimbra, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Gomes
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Girão
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro , 3810-193 Aveiro, Portugal.
authors.forename: José A S
authors.initials: JA
authors.lastname: Cavaleiro
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.
authors.forename: Carlos A F
authors.initials: CA
authors.lastname: Ribeiro
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro , 3810-193 Aveiro, Portugal.|CQE, Instituto Superior Técnico, Universidade de Lisboa , Avenue Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: João P C
authors.initials: JP
authors.lastname: Tomé
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra , 3000-548 Coimbra, Portugal.|CNC.IBILI, Faculty of Medicine, University of Coimbra , 3004-504 Coimbra, Portugal.|Center of Investigation in Environment, Genetics, and Oncobiology , 3001-301 Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000528:radiation effects; D005690:Galactose / Q000737:chemistry*; D037483:Galectin 1 / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D012709:Serum Albumin / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D037483:Galectin 1; D051272:Glucose Transporter Type 1; D017319:Photosensitizing Agents; D011166:Porphyrins; D012709:Serum Albumin; C006969:chlorin; D005690:Galactose