Issue 14, 2022

The uptake of metal–organic frameworks: a journey into the cell


The application of metal–organic frameworks (MOFs) in drug delivery has advanced rapidly over the past decade, showing huge progress in the development of novel systems. Although a large number of versatile MOFs that can carry and release multiple compounds have been designed and tested, one of the main limitations to their translation to the clinic is the limited biological understanding of their interaction with cells and the way they penetrate them. This is a crucial aspect of drug delivery, as MOFs need to be able not only to enter into cells but also to release their cargo in the correct intracellular location. While small molecules can enter cells by passive diffusion, nanoparticles (NPs) usually require an energy-dependent process known as endocytosis. Importantly, the fate of NPs after being taken up by cells is dependent on the endocytic pathways they enter through. However, no general guidelines for MOF particle internalization have been established due to the inherent complexity of endocytosis as a mechanism, with several factors affecting cellular uptake, namely NP size and surface chemistry. In this review, we cover recent advances regarding the understanding of the mechanisms of uptake of nano-sized MOFs (nanoMOFs)s, their journey inside the cell, and the importance of biological context in their final fate. We examine critically the impact of MOF physicochemical properties on intracellular trafficking and successful cargo delivery. Finally, we highlight key unanswered questions on the topic and discuss the future of the field and the next steps for nanoMOFs as drug delivery systems.

Graphical abstract: The uptake of metal–organic frameworks: a journey into the cell

Article information

Article type
Review Article
18 Mar 2022
First published
30 Jun 2022
This article is Open Access
Creative Commons BY license

Chem. Soc. Rev., 2022,51, 6065-6086

The uptake of metal–organic frameworks: a journey into the cell

E. Linnane, S. Haddad, F. Melle, Z. Mei and D. Fairen-Jimenez, Chem. Soc. Rev., 2022, 51, 6065 DOI: 10.1039/D0CS01414A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity