Red-Light Photocatalytic Activation Of Pt(IV) Anticancer Prodrugs Using Methylene Blue

  1. Carrasco, Ana C. 1
  2. Bajetto, Greta 67
  3. Scoditti, Stefano 4
  4. Pieslinger, German E. 5
  5. Gambino, Francesco 1
  6. De Andrea, Marco 67
  7. Sicilia, Emilia 4
  8. Martínez-Martínez, Virginia 8
  9. Dell’Oste, Valentina 6
  10. Salassa, Luca 123
  1. 1 Donostia International Physics Center
    info

    Donostia International Physics Center

    San Sebastián, España

    ROR https://ror.org/02e24yw40

  2. 2 Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV/EHU
  3. 3 Ikerbasque, Fundación Vasca para la Ciencia
    info

    Ikerbasque, Fundación Vasca para la Ciencia

    Bilbao, España

    ROR https://ror.org/01cc3fy72

  4. 4 Department of Chemistry and Chemical Technologies, University of Calabria
  5. 5 CONICET – Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB)
  6. 6 Department of Public Health and Pediatric Sciences, University of Turin
  7. 7 CAAD Center for Translational Research on Autoimmune and Allergic Disease, University of Piemonte Orientale
  8. 8 Departamento de Química Física, Universidad del País Vasco, UPV/EHU
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Revista:
ChemRxiv

Año de publicación: 2024

Tipo: Documento de Trabajo

DOI: 10.26434/CHEMRXIV-2024-LJQRL GOOGLE SCHOLAR lock_openAcceso abierto editor

Resumen

Catalysis-based approaches offer versatile strategies for activating anticancer prodrugs, potentially allowing precise control over drug release and localization within tumor tissues, while reducing systemic toxicity. In this study, we explore the role of the phenothiazine dye methylene blue (MB+) as a photocatalyst in conjunction with biologically relevant electron donors to facilitate the red-light conversion of two Pt(IV) complexes, denoted as cis,cis,trans-[PtCl2(NH3)2(O2CCH2CH2COOH)2] (1) and trans-[Pt(O2CCH2CH2COOH)21R,2R-(DACH)(ox)] (2), into cisplatin and oxaliplatin, respectively. Combining spectroscopic techniques (NMR, UV-Vis, flash photolysis) with computational methods, we reveal that the doubly reduced MB+ (leucomethylene blue, LMB) triggers the reductive elimination of axial ligands in the two Pt(IV) precursors, generating the corresponding Pt(II) anticancer drugs. In vitro experiments conducted on the human cervical cancer cell line CaSki, which harbors multiple copies of the integrated HPV-16 genome, and on non-tumoral cells (HaCat) demonstrate that co-administration with Pt(IV) prodrugs improves MB+'s antiproliferative efficacy in cancer cells, particularly under red light exposure. This enhancement arises from the catalytic production of Pt(II) species within the cellular environment.