Flavins can act as efficient photocatalysts for the conversion of Pt(IV) complexes into Pt(II) anticancer drugs such as cisplatin and carboplatin (Chem. Sci., 2017, 8, 4619; Angew. Chem. Int. Ed., 2018, 57, 3143; ACS Catal., 2020, 10, 187). These unconventional catalytic reactions are bioorthogonal. Thus, they occur with high selectivity in biological environments, with minimal off target reactions. Nevertheless, advancing the application of this original chemistry in chemotherapy requires an optimal co-localization of the flavin catalyst and Pt(IV) substrate in cells or tissues in order to control the release of active Pt(II) drugs upon photocatalytic activation.
To this end, DELCAT proposes the covalent entrapment of Pt(IV) anticancer complexes and flavins, such as riboflavin and its functionalized derivatives, into biocompatible agarose (AG) and polyglycerol (PG) hydrogels. The functionalization versatility of these polymers is ideal for the development of drug delivery platforms that could display various loading capacities, pharmacokinetics and drug release profiles. Hence, the project will engineer AG and PG hydrogels of different structure for loading flavins and Pt(IV) prodrugs, and then assess the drug delivery capacity of these materials in skin tissues. Ultimately, the project will provide innovative photocatalytic polymeric biomaterials for the efficient administration of platinum-based anticancer drugs.
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