Self-assembled multifunctional core-shell highly porous metal-organic framework nanoparticles.

Core-shell nanoparticles (NPs) are attracting increasing interest in nanomedicine as they exhibit unique properties arising from the combined assets of core and shell materials. Porous nanoscale metal–organic frameworks (nanoMOFs) are able to incorporate with high payloads a large variety of drugs. Like other types of NPs, nanoMOFs need to be functionalized with engineered coatings to ensure colloidal stability, control in vivo fate and drug release. To do so, a novel biodegradable cyclodextrin (CD)-based shell was designed in this study. Water soluble γ-CD-citrate oligomers grafted or not with fluorophores were successfully synthesized using citric acid as crosslinker and efficiently anchored onto the surface of porous nanoMOFs. As compared to monomeric CDs, the oligomeric CD coatings could offer higher interaction possibilities with the cores and better possibilities to graft functional moieties such as fluorescent molecules. The amounts of γ-CD-citrate oligomers onto the nanoMOFs were as high as 53 ± 8 wt%. The yield reached up to 86% in the optimized system. These core–shell nanocomposites were stable upon storage, in contrast to the naked nanoMOFs. In addition, the presence of the coating prevented the doxorubicin (DOX)-loaded nanoMOFs from aggregation. Moreover, due to the presence of fluorophores conjugated to the shell, fluorescence-lifetime microscopy enabled deciphering the coating mechanism. DOX loadings reached 48 ± 10 wt% after 24 h incubation with the drug solution. After coating for additional 24 h, DOX loadings reached 65 ± 8 wt%.