2. Academic Validation
  3. Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks

  • J Med Chem. 2020 Sep 10;63(17):9650-9659. doi: 10.1021/acs.jmedchem.0c00781.
Ana M Pérez-López 1,  Belén Rubio-Ruiz 1,  Teresa Valero 1,  Rafael Contreras-Montoya 2,  Luis Álvarez de Cienfuegos 2,  Víctor Sebastián 3 4,  Jesús Santamaría 3 4,  Asier Unciti-Broceta 1
Affiliations

Affiliations

  • 1 Cancer Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, U.K.
  • 2 Departamento de Quı́mica Orgánica, Facultad de Ciencias, Universidad de Granada, Campus de Fuentenueva s/n, Granada 18002, Spain.
  • 3 Department of Chemical Engineering and Environmental Technology; Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza 50009, Spain.
  • 4 Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER- BBN), Madrid 28029, Spain.
PMID: 32787091 DOI: 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. Toward 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.

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