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Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

Authors
  • Pérez-López, Ana M.1
  • Rubio-Ruiz, Belén1
  • Valero, Teresa1
  • Contreras-Montoya, Rafael2
  • Álvarez de Cienfuegos, Luis2
  • Sebastián, Víctor3, 4
  • Santamaría, Jesús3, 4
  • Unciti-Broceta, Asier1
  • 1 University of Edinburgh, U.K.
  • 2 Universidad de Granada, Spain , (Spain)
  • 3 CSIC-Universidad de Zaragoza, Spain , (Spain)
  • 4 Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER- BBN), Spain , (Spain)
Type
Published Article
Journal
Journal of Medicinal Chemistry
Publisher
American Chemical Society
Publication Date
Aug 05, 2020
Volume
63
Issue
17
Pages
9650–9659
Identifiers
DOI: 10.1021/acs.jmedchem.0c00781
PMID: 32787091
PMCID: PMC7497487
Source
PubMed Central
License
Unknown

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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