Toward Supramolecular Nanozymes for the Photocatalytic Activation of Pt(IV) Anticancer Prodrugs

A supramolecular nanozyme for the photocatalytic conversion of a Pt(IV) anticancer complex to cisplatin is described herein. We employed 1.9 nm Au nanoparticles decorated with thiol ligands bearing a TACN (1,4,7-triazacyclononane) headgroup to encapsulate FMN (riboflavin-5'-phosphate). In the presence of an electron donor, flavin-loaded nanoparticles photocatalyzed the reductive activation of the prodrug cis,cis,trans-[Pt(NH3)(2)(Cl-2)(O2CCH2CH2COOH)(2)] to cisplatin, achieving turnover frequency values of 7.4 min(-1).We acknowledge financial support from the Spanish State Research Agency for the grants CTQ2016-80844-R, BIO201677367-R, PID2019-111649RB-I00 and PCI2018-092984. This work was performed under the Severo Ochoa Centres of Excellence and Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency -Grant No. CEX2018-000867-S (DIPC) and MDM-2017-0720 (CIC biomaGUNE). We also thank Fondazione Cariparo (Ricerca Scientifica di Eccellenza Grant "SELECT''). A. M. has received funding from the European Union's Horizon 2020 Research and Innovation Programme under Marie SklodowskaCurie Actions grant no. 793702. We thank the Spanish MultiMetDrugs network (RED2018-102471-T) for fruitful discussion