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.
Highlights
Metal–organic frameworks (MOFs)[1] are a new generation of highly porous macromolecular structures composed of metal ions or clusters linked by multidentate organic bridging ligands, which, owing to their attractive properties, have notable potential for applications in different contexts, including gas capture, storage and separation,[2] catalysis,[3] water treatment[4] and drug delivery.[5]
We and others have shown that UiO-66 is biocompatible,[8c,19] while the cytotoxicity of DCA-loaded MOFs is dependent on surface chemistry,[14c,d] and incorporation of a second drug can dramatically enhance overall cytotoxicity.[15]
While 5-FU loading resulted in ca. 1.2 % (w/w) incorporation with minimal DCA leakage, as determined by ICP-OES, postsynthetic loading of drugs containing metalbinding units resulted in partial or total displacement of DCA (Table S1), as determined by 1H NMR spectroscopic analysis of acid-digested samples, suggesting their loading occurs through attachment to the Zr positions rather than pore storage
Summary
Metal–organic frameworks (MOFs)[1] are a new generation of highly porous macromolecular structures composed of metal ions or clusters linked by multidentate organic bridging ligands, which, owing to their attractive properties, have notable potential for applications in different contexts, including gas capture, storage and separation,[2] catalysis,[3] water treatment[4] and drug delivery.[5]. MOFs have been proposed as an attractive alternative to mitigate drawbacks that other drug delivery systems (DDSs) face,[5,8] as they can exhibit low toxicity, good clearance, high drug loadings, and are easy to functionalise, yet examples of MTV-MOFs for drug delivery applications are still limited.[9] The coordination modulation (CM) protocol[10]—in which monotopic ligands (modulators) compete with the MOF linkers for metal cluster coordination sites during synthesis— has been widely studied to control physical properties such as size,[11] crystallinity, colloidal dispersion,[12] stability and porosity (through defect chemistry),[13] while we have recently shown that it can be used to control MOF surface chemistry and functionality.[14] we have introduced the. We believe that the MTVM protocols could be applied to a wide range of modulators for alternative enhanced applications such as catalysis and gas adsorption/ separation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
