Platinum(II) ring-fused chlorins as efficient theranostic agents: Dyes for tumor-imaging and photodynamic therapy of cancer

Mafalda Laranjo; Márcia Campos Aguiar; Nelson A M Pereira; Gonçalo Brites; Bruno F O Nascimento; Ana F Brito; João Casalta-Lopes; Ana Cristina Gonçalves; Ana Bela Sarmento-Ribeiro; Marta Pineiro; Maria Filomena Botelho; Teresa M V D Pinho E Melo

doi:10.1016/j.ejmech.2020.112468

Platinum(II) ring-fused chlorins as efficient theranostic agents: Dyes for tumor-imaging and photodynamic therapy of cancer

Eur J Med Chem. 2020 Aug 15:200:112468. doi: 10.1016/j.ejmech.2020.112468. Epub 2020 May 16.

Affiliations

¹ University of Coimbra, Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Portugal; University of Coimbra, Clinical and Academic Centre of Coimbra, Portugal.
² University of Coimbra, Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Portugal; University of Coimbra, Coimbra Chemistry Centre and Department of Chemistry, 3004-535, Coimbra, Portugal.
³ University of Coimbra, Coimbra Chemistry Centre and Department of Chemistry, 3004-535, Coimbra, Portugal.
⁴ University of Coimbra, Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Portugal.
⁵ University of Coimbra, Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Portugal; Coimbra Hospital and Universitary Centre, Radiation Oncology Service, Coimbra, Portugal.
⁶ University of Coimbra, Laboratory of Oncobiology and Hematology and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Portugal.
⁷ University of Coimbra, Coimbra Chemistry Centre and Department of Chemistry, 3004-535, Coimbra, Portugal. Electronic address: tmelo@ci.uc.pt.

PMID: 32512486
DOI: 10.1016/j.ejmech.2020.112468

Abstract

The discovery of Pt-chlorin-type theranostic agents is described. Luminescent Pt(II) 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, with different degrees of hydrophilicity, have been synthesized and their in vitro photocytotoxicity against human melanoma, oesophageal and bladder carcinomas was studied. A di(hydroxymethyl)-substituted chlorin was identified as a privileged molecule to explore imaging-guided photodynamic therapy. In addition to the high activity as PDT agent and absence of cytotoxicity per se, this molecule showed the ideal photophysical and photochemical properties. In vivo studies using a A375 melanoma mouse model, proved the extraordinary properties of this chlorin as a luminescent probe and the ability to impair tumor growth, making image guided treatment and follow up a possibility.

Keywords: Animal models; Bladder carcinoma; Luminescence imaging; Melanoma; Oesophageal carcinoma; Optical imaging; Photodynamic therapy; Photosensitizers; Pt(II) chlorins; Theranostics.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry
Coordination Complexes / pharmacology
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Esophageal Neoplasms / drug therapy*
Esophageal Neoplasms / pathology
Fluorescent Dyes / chemical synthesis
Fluorescent Dyes / chemistry
Fluorescent Dyes / pharmacology*
Humans
Melanoma / drug therapy*
Melanoma / pathology
Molecular Structure
Optical Imaging*
Photochemotherapy*
Platinum / chemistry
Platinum / pharmacology
Porphyrins / chemistry
Porphyrins / pharmacology
Structure-Activity Relationship
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / pathology

Substances

Antineoplastic Agents
Coordination Complexes
Fluorescent Dyes
Porphyrins
chlorin
Platinum