Multivariate Modulation of the Zr MOF UiO‐66 for Defect‐Controlled Combination Anticancer Drug Delivery

Abstract

Metal–organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination to the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis.

Metal-Organic Frameworks: A Potential Platform for Enzyme Immobilization and Related Applications

“…Metal-Organic Frameworks (MOFs) are composed of metal nodes and organic ligands connected through coordination bonds, which shows great potential in various applications ( Kleist et al, 2010 ; Cho et al, 2012 ; Ding et al, 2019 ; Masoomi et al, 2019 ; Shi et al, 2019 ; Wang et al, 2019 ; Yilmaz et al, 2019 ; Abanades Lazaro et al, 2020 ; Bonneau et al, 2020 ; Cruz-Navarro et al, 2020 ). Given that the topology and property of MOFs could be tuned for their multiple metal nodes and ligands, interactions such as hydrogen bonding, van der Waals forces, covalence, and coordinative bonding between MOFs support and enzyme are possible ( Majewski et al, 2017 ).…”

Carbon Dots Based Nanoscale Covalent Organic Frameworks for Photodynamic Therapy

“…Recently, porous materials, especially metal‐organic frameworks (MOFs), are widely used in drug delivery and bioimaging due to the various structures and multiple functions. [ 1–8 ] Relatively, covalent organic frameworks (COFs) formed purely from organic monomers are less explored in biomedical fields due to the large size, low aqueous dispersivity, and poor cell permeability, although they possess unique characters of potential biodegradability in vivo and the low density. [ 9–11 ] Most of the reported COFs are made from aromatic molecules with several functional groups, such as amino, aldehyde, or boric acid.…”

Review of the Biomolecular Modification of the Metal-Organ-Framework

“…MOF formation occurs because of the coordination between metal atoms and the organism, and different numbers and categories of metals or organic compounds will produce a variety of constructs, such as those resulting from bimetallic organism synthesis. Recently, a new multivariate modulation of Zr-MOF UiO-66 (Abanades Lazaro et al, 2020 ) was reported. Multivariate modulation allows the incorporation of up to three drugs containing either carboxylates or phosphates as metal-binding units to coordinate with the defect sites of metal clusters in UiO-66.…”

“…As porous nanomaterials, MOFs are capable of high loading capacities, controlled release, plasticity, and biosafety, which facilitate the selective transportation of nanomaterials through the porous network (An et al, 2012 ). MOFs have been proposed as an attractive alternative to mitigate drawbacks that other drug delivery systems (DDSs) face (Abanades Lazaro et al, 2020 ). Thus, MOFs have already served as a successful drug delivery platform (Zhao et al, 2011 ).…”