Bioorthogonal Photocatalytic Activation of Metal-Based Prodrugs

Informations projet

ORTHOCAT

N° de convention de subvention: 793702

DOI

10.3030/793702

Projet clôturé

Date de signature de la CE 19 Mars 2018

Date de début 10 Septembre 2018

Date de fin 9 Septembre 2020

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 158 121,60

Contribution de l’UE

€ 158 121,60

Coordonné par

FUNDACION DONOSTIA INTERNATIONAL PHYSICS CENTER
Spain

Periodic Reporting for period 1 - ORTHOCAT (Bioorthogonal Photocatalytic Activation of Metal-Based Prodrugs)

Période du rapport: 2018-09-10 au 2020-09-09

Résumé du contexte et des objectifs généraux du projet

Anticancer treatments frequently result in undesired side effects with high impact in the life quality of chemotherapy patients. One approach to minimize this effect is administrating an inactive version of the drug (prodrug) and converting it into the active drug directly, and only, in the tumor area. One of the ways to perform drug activation is by irradiating the prodrug with light. We recently discovered that riboflavin (vitamin B2) irradiated with blue light facilitates the transformation of platinum prodrugs intro cisplatin, one of the most used anticancer drugs in the clinics. Such flavin-mediated reaction is catalytic and occurs with high selectivity even in complex biological environments (i.e. bioorthogonality). The objectives of ORTHOCAT is to develop a system containing the different components (platinum prodrug and flavin) capable to perform this transformation as a single unit in cells and result in anticancer activity with low side effects. We would employ gold nanoparticles as vehicles to carry all the catalysis components.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

We have been able to prepare gold nanoparticle systems that were capable of binding both a flavin catalyst and different platinum prodrugs. We explored combinations of these components and selected the system with the best performance. The system was able to produce the anticancer compound (cisplatin) after only few minutes of blue light irradiation and resulting in an improved photostability of the flavin catalyst.
The results been disseminated in one scientific publication (Chem. Commun., 2020, 56, 10461, being highlighted with a cover image) and four presentations in scientific conferences. In addition, we have shared our findings in a dedicated webpage for the project as well as on Twitter. The researcher has also participated to four outreach activities.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The system developed in this project is the first nanoplatform employing a vitamin derivative (riboflavin, B2) as photocatalyst for the activation of Pt anticancer prodrugs. Further work is needed to assess the full potential of the project’s strategy in complex biological models. Nevertheless, the results obtained by ORTHOCAT demonstrate that the approach employed allows to control spatio-temporally the effects of Pt anticancer drugs via light activation and catalytic amplification. Overall, this could open a new path towards the development of anticancer treatments with diminished side effects.

Schematic overview of the project strategy

Molecular structure of the main components