Porous Metal–Organic Frameworks as New Drug Carriers

Abstract

The easy tunable composition (metal or organic linker) and topology (porosity, connectivity, …) of porous crystalline hybrid solids or MOFs (metal–organic frameworks) make biocompatible MOFs very attractive candidates for biomedical applications. Their biodegradable character, confirmed by in vitro experiments, can be modulated from a few hours to weeks by tuning their composition and/or topology, avoiding thus their accumulation within the body. Some iron carboxylates-based MOFs have been proven to be nontoxic even after intravenous administration of high doses in rats. The amphiphilic internal microenvironment of MOFs is well adapted to accommodate a large number of guest molecules with therapeutic activity. In fact, MOFs showed unprecedented loading capacities of therapeutic molecules in comparison to other carriers (polymers, zeolites, …), with controlled release kinetics under physiological conditions. Therapeutic activity can also be introduced in MOFs by directly using an active molecule within the hybrid framework: (1) either as the organic linker, releasing thus the bioactive molecule though the degradation of the framework or (2) as an active metal (Gd, Mn, Fe, …), leading to interesting imaging properties useful for theranostics. Finally, considering the different administration routes required for biomedical applications, several formulations based on MOFs are possible, including (1) pellets or tablets, (2) thin films for patches, (3) composite materials based either on polymers or inorganic matrix (creams, silica-cover MOFs, etc.), or (4) stable colloidal suspensions of nanoparticles with engineered surfaces. Stealth, addressing or imaging properties of MOFs nanoparticles can be ensured through surface modifications with various organic biomolecules (poly(ethylen glycol) (PEG), chitosan, …), either during or after the synthesis.