Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks
- 5 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 63 (17), 9650-9659
- https://doi.org/10.1021/acs.jmedchem.0c00781
Abstract
The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts, but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Towards this goal, here we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.Keywords
Funding Information
- Engineering and Physical Sciences Research Council (EP/N021134/1)
- Ministerio de Ciencia, Innovaci?n y Universidades (RTI2018-099019-A-I00)
- European Regional Development Fund (FIS2017-85954-R)
- Universidad de Granada
- H2020 Marie Sklodowska-Curie Actions (658833, 749299)
- H2020 European Research Council (742684)
- Junta de Andalucía (P12-FQM-790)
- Agencia Estatal de Investigación
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