Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light.
Inorg Chem
; 63(15): 6822-6835, 2024 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-38560761
ABSTRACT
Boron-dipyrromethene (BODIPY) dyes are promising photosensitizers for cellular imaging and photodynamic therapy (PDT) owing to their excellent photophysical properties and the synthetically tunable core. Metalation provides a convenient way to overcome the drawbacks arising from their low aqueous solubility. New photo-/redox-responsive Co(III) prodrug chaperones are developed as anticancer PDT agents for efficient cellular delivery of red-light-active BODIPY dyes. The photobiological activity of heteroleptic Co(III) complexes derived from tris(2-pyridylmethyl)amine (TPA) and acetylacetone-conjugated PEGylated distyryl BODIPY (HL1) or its dibromo analogue (HL2), [CoIII(TPA)(L1/L2)](ClO4)2 (1 and 2), are investigated. The Co(III)/Co(II) redox potential is tuned using the Co(III)-TPA scaffold. Complex 1 displays the in vitro release of BODIPY on red light irradiation. Complex 2, having good singlet oxygen quantum yield (ΦΔ â¼ 0.28 in DMSO), demonstrates submicromolar photocytotoxicity to HeLa cancer cells (IC50 ≈ 0.23 µM) while being less toxic to HPL1D normal cells in red light. Cellular imaging using the emissive complex 1 shows mitochondrial localization and significant penetration into the HeLa tumor spheroids. Complex 2 shows supercoiled DNA photocleavage activity and apoptotic cell death through phototriggered generation of reactive oxygen species. The Co(III)-BODIPY prodrug conjugates exemplify new type of phototherapeutic agents with better efficacy than the organic dyes alone in the phototherapeutic window.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Porfobilinogênio
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Pró-Fármacos
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Inorg Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia