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

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Demir Duman, Fatma, Monaco, Alessandra, Foulkes, Rachel, Becer, C. Remzi and Forgan, Ross 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 ISSN 2574-0970.

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Official URL: https://doi.org/10.1021/acsanm.2c01632

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Abstract

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: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Cancer -- Research, Organometallic polymers, Drug delivery systems, Polymerization, Polymers in medicine
Journal or Publication Title: ACS Applied Nano Materials
Publisher: American Chemical Society (ACS)
ISSN: 2574-0970
Official Date: 28 October 2022
Dates:
DateEvent
28 October 2022Published
22 June 2022Available
6 June 2022Accepted
Volume: 5
Number: 10
Page Range: pp. 13862-13873
DOI: 10.1021/acsanm.2c01632
Status: Peer Reviewed
Publication Status: Published
Reuse Statement (publisher, data, author rights): ** Article version: VoR ** From Crossref journal articles via Jisc Publications Router ** History: epub 22-06-2022; issued 22-06-2022. ** Licence for VoR version of this article starting on 22-06-2022: https://creativecommons.org/licenses/by/4.0/
Access rights to Published version: Open Access (Creative Commons)
Copyright Holders: © 2022 The Authors. Published by American Chemical Society
Date of first compliant deposit: 4 August 2022
Date of first compliant Open Access: 4 August 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
677289[ERC] Horizon 2020 Framework Programmehttp://dx.doi.org/10.13039/100010661
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