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.

Anti-inflammatory and antioxidant effects of nanoformulations composed of metal-organic frameworks delivering rutin and/or piperine natural agents

“…Several studies suggest that MOFs of various types show great promise in drug delivery of, e.g. anticancer, anti-inflammatory, and antibacterial agents (Dong et al, 2018;Li et al, 2019b;Nasrabadi et al, 2019;Ab anades L azaro et al, 2020;Lu et al, 2020). An important and unique feature of MOFs as carriers is their low toxicity and their enhancement of bioavailability and solubility of the drug.…”

Cracking the Chloroquine Conundrum: The Application of Defective UiO-66 Metal–Organic Framework Materials to Prevent the Onset of Heart Defects—In Vivo and In Vitro

“…Of the numerous metal–organic frameworks with potential use as drug delivery systems, Zn-, Fe-, Zr-, and Mg-based metal–organic frameworks are being researched intensely due to their low cytotoxicity, high biodegradability, and high biocompatibility. 7 , 10 , 12 − 16 Among the numerous groups of possible MOFs with various topologies, the zirconium-based metal–organic framework UiO-66 (Universitetet i Oslo) composed of octahedron clusters [Zr 6 O 4 (OH) 4 ] and 1,4-benzenedicarboxylic acid ligands meets the requirements for drug carriers. Due to its properties, such as high thermal and physical properties, high surface area, and a high degree of freedom in synthesis and postsynthesis, its potential for modification has attracted considerable attention in terms of its potential as a drug delivery carrier.…”

“…Due to its properties, such as high thermal and physical properties, high surface area, and a high degree of freedom in synthesis and postsynthesis, its potential for modification has attracted considerable attention in terms of its potential as a drug delivery carrier. 12 − 15 In the work by Jarai et al, 13 composite dexamethasone@UiO-66 and rhodamien@UiO-66 were determined as novel drug delivery systems for pulmonary diseases. It was found that the modulated synthesis of 100 nm crystals of UiO-66 does not affect the aerodynamics of NPs in aerosols and has a negligible effect on drug loading.…”

“…The in vitro cytotoxicity tests revealed low cytotoxicity of Zr-based MOFs and high tolerance in murine in vivo tests. Another example of modulated synthesis of UiO-66 was presented in the work by Lázaro et al 12 In this work, dichloroacetic acid and hydrochloric acid were used as a modulator during the synthesis of defective UiO-66. The UiO-66 crystal synthesized by the addition of 10 equiv of CHCl 2 COOH and 1 equiv of HCl during the solvothermal synthesis allowed the synthesis of UiO-66 crystals with considerably increased contribution of pores >10 Å.…”

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

“…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).…”