Guest Leakage from ZIF-8 Particles under Drug Delivery Conditions: Quantitative Characterization and Guest-Induced Framework Stabilization

Metal–organic frameworks (MOFs) are promising nanomaterials for the construction of stimuli–responsive drug delivery platforms. The counterpart of the incredible sensitivity of MOFs to pathological conditions, which underpins targeted drug release, is the significant instability of nanoparticles even in normal physiological media. We report a new experimental approach for quantitative characterization of the guest release profile from MOF ZIF-8 (zeolitic imidazolate framework) suspensions under drug delivery conditions. For this sake, we used ZIF-8 with encapsulated stable nitroxides, which was exposed to physiological media, and the in situ kinetics of guest escape was monitored by electron paramagnetic resonance (EPR). The release of spin probes drastically changes the EPR spectral shapes, thus allowing quantitative characterization of leaked species. We demonstrate that the guest release from ZIF-8 particles in blood-mimicking solutions is a concentration-dependent process dictated by albumin, and nearly full guest release from nanoparticles in fetal bovine serum (FBS) occurs within a few minutes. Significant deceleration of this process and stabilization of ZIF-8 in FBS can be achieved by additional adsorption of guest inhibitors (exemplified by aromatic hydrocarbons) prior to contact with physiological media. The proposed methodology provides further perspectives for optimization of MOF-based platforms for efficient drug delivery.