Glycopolymer-functionalized MOF-808 nanoparticles as a cancer-targeted dual drug delivery system for carboplatin and floxuridine

Demir Duman, F. , Monaco, A., Foulkes, R., Becer, C. R. and Forgan, R. S. (2022) Glycopolymer-functionalized MOF-808 nanoparticles as a cancer-targeted dual drug delivery system for carboplatin and floxuridine. ACS Applied Nano Materials, 5(10), pp. 13862-13873. (doi: 10.1021/acsanm.2c01632) (PMID:36338327) (PMCID:PMC9623548)

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Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal–organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Foulkes, Miss Rachel and Forgan, Professor Ross and Demir Duman, Dr Fatma
Authors: Demir Duman, F., Monaco, A., Foulkes, R., Becer, C. R., and Forgan, R. S.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:ACS Applied Nano Materials
Publisher:American Chemical Society
ISSN (Online):2574-0970
Published Online:22 June 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in ACS Applied Nano Materials 5(10): 13862-13873
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