Metal substrate catalysis in the confined space for platinum drug delivery. Issue 1 (29th November 2021)

• Record Type: Journal Article
• Authors: Velasco-Lozano, Susana; Castro, Silvia Alonso-de; Sanchez-Cano, Carlos; Benítez-Mateos, Ana I.; López-Gallego, Fernando; Salassa, Luca
• Is Part Of: Chemical science. Volume 13:Issue 1(2022)
• Page Start: 59
• Page End: 67
• Publication Date: 2021-11-29
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc05151b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Loading of a flavin catalyst and Pt prodrug onto a hydrogel affords biomaterials for the catalytic generation and delivery of cisplatin upon light irradiation or addition of electron donors. Confinement boosts the turnover frequency of the flavin. Abstract : Catalysis-based approaches for the activation of anticancer agents hold considerable promise. These principally rely on the use of metal catalysts capable of deprotecting inactive precursors of organic drugs or transforming key biomolecules available in the cellular environment. Nevertheless, the efficiency of most of the schemes described so far is rather low, limiting the benefits of catalytic amplification as strategy for controlling the therapeutic effects of anticancer compounds. In the work presented here, we show that flavin reactivity within a hydrogel matrix provides a viable solution for the efficient catalytic activation and delivery of cisplatin, a worldwide clinically-approved inorganic chemotherapy agent. This is achieved by ionically adsorbing a flavin catalyst and a Pt(iv ) prodrug as substrate into porous amino-functionalized agarose beads. The hydrogel chassis supplies high local concentrations of electron donating groups/molecules in the surrounding of the catalyst, ultimately boosting substrate conversion rates (TOF >200 min −1 ) and enabling controlled liberation of the drug by light or chemical stimuli. Overall, this approach can afford platforms for the efficient delivery of platinum drugs as demonstrated herein by using a transdermal diffusion model simulating the human skin.