Green Light Activated Dual-Action Pt(IV) Prodrug with Enhanced PDT Activity
Light induced release of cisplatin from Pt(IV) prodrugs is a promising tool for precise spatiotemporal control over the antiproliferative activity of Pt-based chemotherapeutic drugs. A combination of light-controlled chemotherapy (PACT) and photodynamic therapy (PDT) in one molecule has the potentia...
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Veröffentlicht in: | ChemMedChem 2025-01, p.e202400786 |
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Sprache: | eng |
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Zusammenfassung: | Light induced release of cisplatin from Pt(IV) prodrugs is a promising tool for precise spatiotemporal control over the antiproliferative activity of Pt-based chemotherapeutic drugs. A combination of light-controlled chemotherapy (PACT) and photodynamic therapy (PDT) in one molecule has the potential to overcome crucial drawbacks of both Pt-based chemotherapy and PDT via a synergetic effect. Herein we report green-light-activated Pt(IV) prodrug GreenPt with BODIPY-based photosentitizer in the axial position with an incredible high light response and singlet oxygen generation ability. GreenPt demonstrated the ability to release cisplatin under low-dose green light irradiation up to 1 J/cm
. The investigation of the photoreduction mechanism of GreenPt prodrug using DFT modeling and ΔG
PET estimation revealed that the anion-radical formation and substituent photoinduced electron transfer from the triplet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin. Green-light-activated BODIPY-based photosentitizers 5 and 8 demonstrated outstanding photosensitizing properties with an extraordinary phototoxicity index (PI)>1300. GreenPt prodrug demonstrated gradual intracellular accumulation and light-induced phototoxicity with PI>100, thus demonstrating dual action through light-controlled release of both cisplatin and a potent BODIPY-based photosensitizer. |
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ISSN: | 1860-7179 1860-7187 1860-7187 |
DOI: | 10.1002/cmdc.202400786 |