Multivariate modulation of the Zr MOF UiO-66 for defect-controlled multimodal anticancer drug delivery

Abánades Lázaro, I., Wells, C. J.R. and Forgan, R. S. (2020) Multivariate modulation of the Zr MOF UiO-66 for defect-controlled multimodal anticancer drug delivery. Angewandte Chemie (International Edition), 59(13), pp. 5211-5217. (doi: 10.1002/anie.201915848) (PMID:31950568) (PMCID:PMC7154787)

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Metal‐organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination at the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis.

Item Type:Articles
Additional Information:RSF acknowledges the Royal Society for a University Research Fellowship.
Glasgow Author(s) Enlighten ID:Abanades, Miss Isabel and Forgan, Professor Ross
Authors: Abánades Lázaro, I., Wells, C. J.R., and Forgan, R. S.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Angewandte Chemie (International Edition)
ISSN (Online):1521-3773
Published Online:17 January 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Angewandte Chemie (International Edition) 2020 59:5211-5217
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172845SCoTMOFRoss ForganEuropean Research Council (ERC)677289Chemistry