Search

Controllable surface modification of nanoparticulate drug delivery vectors is key to enhancing specific desirable properties such as colloidal stability, targeting, and stimuli-responsive cargo release. Metal-organic frameworks (MOFs) have been proposed as potential delivery devices, with surface modification achieved by various bioconjugate "click" reactions, including copper-catalysed and strain-promoted azide-alkyne cycloaddition. Herein, we show that photo-induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) can be used to surface-modify tetrazole-appended Zr MOFs with maleimides, and vice versa, with the extent of this traceless surface functionalisation controlled by the length of photoirradiation. This "photoclick" surface modification protocol is exemplified by the decorating of carboplatin-loaded MOF-808 with galactose units to target asialoglycoprotein receptors of specific cancer cell types. Targeting towards HepG2 cells, which overexpress these receptors, is indicated by enhanced endocytosis and cytotoxicity in both two- and three-dimensional cell cultures compared to other cell lines. The study shows both the power of the NITEC protocol for functionalisation of MOFs, and also the benefits of carbohydrate targeting in drug delivery vectors, with scope for significant additional work diversifying the surface targeting units available for nanoparticle functionalisation under these mild, biocompatible "photoclick" conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ross Forgan reports financial support was provided by Engineering and Physical Sciences Research Council. Yang Wang reports financial support was provided by China Scholarship Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nanoscale metal-organic frameworks (NMOFs) are an interesting and unique class of hybrid porous materials constructed by the self-assembly of metal ions/clusters with organic linkers. The high storage capacities, facile synthesis, easy surface functionalization, diverse compositions and excellent biocompatibilities of NMOFs have made them promising agents for theranostic applications. By combination of a large variety of metal ions and organic ligands, and incorporation of desired molecular functionalities including imaging modalities and therapeutic molecules, diverse MOF structures with versatile functionalities can be obtained and utilized in biomedical imaging and drug delivery. In recent years, NMOFs have attracted great interest as imaging agents in optical imaging (OI), magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and photoacoustic imaging (PAI). Furthermore, the significant porosity of MOFs allows them to be loaded with multiple imaging agents and therapeutics simultaneously and applied for multimodal imaging and therapy as a single entity. In this review, which is intended as an introduction to the use of MOFs in biomedical imaging for a reader entering the subject, we summarize the up-to-date progress of NMOFs as bioimaging agents, giving (i) a broad perspective of the varying imaging techniques that MOFs can enable, (ii) the different routes to manufacturing functionalised MOF nanoparticles and hybrids, and (iii) the integration of imaging with differing therapeutic techniques. The current challenges and perspectives of NMOFs for their further clinical translation are also highlighted and discussed.

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., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity. Tuning particle size and, more significantly, surface chemistry, further improves cytotoxicity by promoting caveolae-mediated endocytosis and cytosolic cargo delivery.