Degradation Mechanism of Metal-Organic Framework Drug Nanocarriers Studied by Solid-State Nuclear Magnetic Resonance and X-ray Absorption Near-Edge Structure Spectroscopy

Metal-organic framework nanoparticles (nanoMOFs) are novel porous drug delivery systems whose features include high drug loading capacity, versatile functionalization, biocompatibility, and biodegradability. However, little knowledge about the nature of nanoMOF degradation mechanism is one of the many reasons that prevent their clinical use. MIL-100 (MIL stands for Materia uxde l'Institut Lavoisier) is among the most studied nanoMOFs for drug delivery. Here, we investigate at the atomic scale the degradation mechanism of metal(III)-trimesate nanoMIL-100 drug carrier in biological-mimicking phosphate medium. By using solid-state NMR (ssNMR) spectroscopy, we found that the first step of nanoMIL-100(Al) degradation is the substitution of labile water ligands, resulting in new coordination bonds between Al(III) and phosphate ions, followed by the substitution of trimesate ligands, leading to their release. The data indicated that the reaction-limiting step most likely is the formation of an inorganic aluminophosphate layer at the nanoparticle surface and that drug encapsulation and surface coating affect the nanoMIL-100(Al) degradation. The X-ray absorption near-edge structure (XANES) spectroscopy study of nanoMIL-100(Fe) degradation corroborates the hypothesized alteration mechanism of nanoMIL-100(Al). From the ensemble of data, a stepwise degradation mechanism representative for the nanoMIL-100 drug delivery system is proposed.