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PreprintCC BY-NCChemRxiv

IN SITU ASSEMBLY OF ACTIVE THERAPEUTICS THROUGH ALBUMIN-MEDIATED METAL TRANSFER

  • Manu Sánchez1
  • Esteban Zingales1,2,3
  • German E. Pieslinger1,4,5,6,7
  • Luisa D’Anna8
  • Itziar Souto-Riobo2,3
  • Jessica Walker9
  • Alessio Terenzi8
  • Susana Carregal-Romero2,10,11,12
  • Carlos Sanchez-Cano1,3,12
12 affiliations
  1. 1Donostia International Physics Center, Paseo Manuel Lardizabal, 4, Donostia / San Sebastián, Spain, 20018
  2. 2Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA)
  3. 3Kimika Fakultatea, Euskal Herriko Unibertsitatea (EHU), Paseo Manuel Lardizabal, 3, Donostia / San Sebastián, Spain, 20018
  4. 4Instituto de Química y Fisicoquímica Biológicas (IQUIFIB)
  5. 5CONICET – Universidad de Buenos Aires.
  6. 6Facultad de Farmacia y Bioquímica
  7. 7Universidad de Buenos Aires
  8. 8Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università degli Studi di Palermo, Viale delle Scienze, Edificio 17, Palermo, Italy, 90128
  9. 9Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom, OX11 0DE
  10. 10Centro de investigación en red de enfermedades respiratorias (CIBERES)
  11. 11Instituto de Salud Carlos III
  12. 12Ikerbasque, Basque Foundation for Science Ikerbasque
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Abstract

Forming active therapeutic agents in situ can be a promising strategy to obtain safer and more effective treatments. However, achieving controlled formation of a drug in complex biological settings requires a detailed understanding of the target environment where the new therapeutic agent will be generated and the use of well-designed activation strategies. Here, we demonstrate that it is possible to form active metal complexes in blood serum and plasma by using ligands that target metal ions transported by albumin after they are bound to the protein. As a proof of concept, we applied this strategy to activate photosensitizers (PS) for photodynamic therapy (PDT). In situ metalation generated photoactivatable complexes with enhanced photochemical properties and anticancer activity, establishing albumin-bound metal ions as an endogenous resource for therapeutic activation.

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Cite

BibTeXRIS
BibTeX
@misc{sanchez2026situ,
  title = {{IN SITU ASSEMBLY OF ACTIVE THERAPEUTICS THROUGH ALBUMIN-MEDIATED METAL TRANSFER}},
  author = {Manu Sánchez and Esteban Zingales and German E. Pieslinger and Luisa D’Anna and Itziar Souto-Riobo and Jessica Walker and Alessio Terenzi and Susana Carregal-Romero and Carlos Sanchez-Cano},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15004045/v4},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004045/v4},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - IN SITU ASSEMBLY OF ACTIVE THERAPEUTICS THROUGH ALBUMIN-MEDIATED METAL TRANSFER
AU  - Manu Sánchez
AU  - Esteban Zingales
AU  - German E. Pieslinger
AU  - Luisa D’Anna
AU  - Itziar Souto-Riobo
AU  - Jessica Walker
AU  - Alessio Terenzi
AU  - Susana Carregal-Romero
AU  - Carlos Sanchez-Cano
PY  - 2026
DA  - 2026/10/25
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15004045/v4
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004045/v4
AB  - Forming active therapeutic agents in situ can be a promising strategy to obtain safer and more effective treatments. However, achieving controlled formation of a drug in complex biological settings requires a detailed understanding of the target environment where the new therapeutic agent will be generated and the use of well-designed activation strategies. Here, we demonstrate that it is possible to form active metal complexes in blood serum and plasma by using ligands that target metal ions transported by albumin after they are bound to the protein. As a proof of concept, we applied this strategy to activate photosensitizers (PS) for photodynamic therapy (PDT). In situ metalation generated photoactivatable complexes with enhanced photochemical properties and anticancer activity, establishing albumin-bound metal ions as an endogenous resource for therapeutic activation.
ER  -