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Catalysis toward platinum substrates for drug delivery

Project description

Delivery and photoactivation of platinum-based prodrugs

The development of photoactivatable platinum-based prodrugs increases the selectivity and lowers the toxicity of antitumour drugs. Photocatalysis by flavins converts the prodrug platinum(IV) complexes into anticancer drugs such as cisplatin or carboplatin. This reaction occurs in biological environments with high targeting specificity and could find use in treating tumours accessible to fibre-optic devices. Funded by the Marie Skłodowska-Curie Actions programme, the DELCAT project aims to develop innovative photocatalytic biomaterials for the efficient delivery of platinum-based anticancer drugs. To that end, it will create agarose and polyglycerol hydrogels loaded with flavins and Pt(IV) prodrugs for the evaluation of delivery capacity and photocatalytic efficiency in skin tissues.

Objective

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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Coordinator

FUNDACION DONOSTIA INTERNATIONAL PHYSICS CENTER
Net EU contribution
€ 160 932,48
Address
Paseo manuel lardizabal 4
20018 Donostia san sebastian
Spain

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Region
Noreste País Vasco Gipuzkoa
Activity type
Research Organisations
Links
Other funding
€ 0,00