Encapsulation and delivery of mitoxantrone using zirconium-based metal–organic frameworks (MOFs) and their cytotoxic potential in breast cancer cells
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2024-02Author
Singhal, M.Riches-Suman, Kirsten

Pors, Klaus

Addicoat, M.A.
Ruiz, Amalia

Nayak, Sanjit

Elies, Jacobo

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© 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/).Peer-Reviewed
YesOpen Access status
openAccessAccepted for publication
2024-02-22
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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 computational 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.Version
Published versionCitation
Singhal M, Riches-Suman K, Pors K et al (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.Link to Version of Record
https://doi.org/10.3390/app14051902Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.3390/app14051902