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.
Keywords: Carboplatin; Click chemistry; Galactose; Metal-organic frameworks; Surface modification; Targeted drug delivery.
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