Encapsulation and delivery of mitoxantrone using zirconium-based Metal–Organic Frameworks (MOFs) and their cytotoxic potential in breast cancer cells

Singhal, M, Riches-Suman, K, Pors, K, Addicoat, MA ORCID: https://orcid.org/0000-0002-5406-7927, Ruiz, A, Nayak, S and Elies, J, 2024. Encapsulation and delivery of mitoxantrone using zirconium-based Metal–Organic Frameworks (MOFs) and their cytotoxic potential in breast cancer cells. Applied Sciences, 14 (5): 1902. ISSN 2076-3417

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Abstract

Mitoxantrone (MTX) is a drug employed in breast cancer treatment, but its application is largely limited due to side effects. A controlled delivery approach can potentially reduce the side effects. In this study, two zirconium (Zr)-based MOFs, UiO-66 and UiO-66-NH2, were studied for a more controlled delivery of MTX with a 40% and 21% loading capacity, respectively. Characterisation via powder X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectrometry, scanning electron microscopy, and dynamic light scattering confirmed the integrity of structure post-MTX loading. UV–vis spectrophotometry revealed distinctive release profiles, with UiO-66-MTX exhibiting a 25% cumulative release after 96 h in water and 120 h in PBS +10% FBS. UiO-66-NH2-MTX displayed a more sustained release, reaching 62% in water and 47% in PBS +10% FBS after 168 h. The interaction between MTX and the MOFs was also proposed based on com-putational modelling, suggesting a stronger interaction of UiO-66NH2 and MTX, and an optimised interaction of MTX in the tetrahedral and octahedral pores of the MOFs. The study also reports the release profile of the drug and antiproliferative activity against a panel of breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF7) and a normal breast epithelial cell line (MCF10A). MTX-encapsulated MOFs were thoroughly characterised, and their biological activity was assessed in vitro. MTT cell viability assay indicated a higher IC50 value for MTX-loaded MOFs compared to free MTX in physiological conditions, albeit with a slower release profile. These findings suggest the potential of these MTX-loaded MOFs as an alternative avenue for formulation to mitigate side effects.

Item Type:	Journal article
Publication Title:	Applied Sciences
Creators:	Singhal, M., Riches-Suman, K., Pors, K., Addicoat, M.A., Ruiz, A., Nayak, S. and Elies, J.
Publisher:	MDPI
Date:	26 February 2024
Volume:	14
Number:	5
ISSN:	2076-3417
Identifiers:	Number Type 10.3390/app14051902 DOI 1869208 Other
Rights:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	01 Mar 2024 14:25
Last Modified:	13 Mar 2024 12:11
URI:	https://irep.ntu.ac.uk/id/eprint/50999

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