Identifying differing intracellular cargo release mechanisms by monitoring in vitro drug delivery from MOFs in real time

Markopoulou, P., Panagiotou, N. , Li, A., Bueno-Perez, R., Madden, D., Buchanan, S., Fairen-Jimenez, D., Shiels, P. G. and Forgan, R. S. (2020) Identifying differing intracellular cargo release mechanisms by monitoring in vitro drug delivery from MOFs in real time. Cell Reports Physical Science, 1, 100254. (doi: 10.1016/j.xcrp.2020.100254)

Abstract

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy. The attenuated release of aggregated doxorubicin from the surface of Dox@UiO-66 results in a 12 to 16 h induction of cytotoxicity, while rapid release of pore-dispersed doxorubicin from Dox@MIL-101(Cr) leads to significantly higher intranuclear localization and rapid cell death. In verifying real-time cell analysis as a versatile tool to assess biocompatibility and drug delivery, we show that the localization of drugs in (or on) MOF nanoparticles controls delivery profiles and is key to understanding in vitro modes of action.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Panagiotou, Dr Nikolaos and Markopoulou, Ms Panagiota and Buchanan, Dr Sarah and Forgan, Professor Ross and Shiels, Professor Paul
• Authors: Markopoulou, P., Panagiotou, N., Li, A., Bueno-Perez, R., Madden, D., Buchanan, S., Fairen-Jimenez, D., Shiels, P. G., and Forgan, R. S.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Cell Reports Physical Science
• Publisher: Elsevier (Cell Press)
• ISSN: 2666-3864
• ISSN (Online): 2666-3864
• Copyright Holders: Copyright © 2020 The Author(s)
• First Published: First published in Cell Reports Physical Science 1:100254
• Publisher Policy: Reproduced under a Creative Commons license
• Data DOI: 10.5525/gla.researchdata.1072

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172845		SCoTMOF	Ross Forgan	European Research Council (ERC)	677289	Chemistry