Magnetic Field-Induced Drug Delivery from ZIF-8 Metal-Organic Frameworks-Based Nanocomposites through Magnetic Nanoparticles Heating or Motion

Metal-organic frameworks (MOFs) hold great promise for drug delivery applications due to their large tuna-ble porosity and structural flexibility, which facilitate designs with high drug-loading capacities and biocom-patibility. Despite these advantages, controlling off-target, uncontrolled drug release remains challenging. This study develops a magnetic field-responsive magnetic nanocomposite based on MOFs to enable spatio-temporal controlled drug delivery. The design features a superparamagnetic iron oxide nanoparticle core and a nanometric zeolitic imidazolate framework (ZIF-8) shell, loaded with cresyl violet as a fluorescent probe and stabilized with a fluorescein-labelled amphiphilic polymer. The nanocomposites demonstrate biocom-patibility up to 1 pM with MiaPaCa-2 cancer cells and cancer-associated fibroblasts (CAF) and preferentially accumulate in endolysosomes. Exposure to high-frequency alternating or low-frequency rotating magnetic fields significantly increases the release of cresyl violet into the cytosol of MiaPaca-2 and CAF cells. This release —whether thermal or mechanical— reduces the viability of cells in 2D culture and the size of 3D spheroids composed of MiaPaCa2 and CAF cells, illustrating precise spatiotemporal control over the drug delivery process. The proposed MOF-based magnetic nanocomposites represent promising platforms for developing magnetic field-responsive drug delivery systems.