Magnetic field-induced drug delivery from magnetic microporous nanocomposites through magnetic nanoparticles heating or motion

• Development of a new magnetic field-controlled drug delivery nanosystem based on a magnetic iron oxide nanoparticle and a metal–organic framework. • Magnetic fields offer spatio-temporal control over drug release • Magnetic fields do not face limitations related to tissue penetration depth. • Induction of drug release through magnetic hyperthermia or mechanical forces. Metal-organic frameworks (MOFs) are promising carriers for drug delivery applications due to their large tunable porosity, structural flexibility, biocompatibility and high drug-loading capacities. Nonetheless, precise, on-demand release remains challenging. Here, we designed a magnetic field-responsive nanocomposite comprising superparamagnetic iron oxide nanoparticles (IONP) coated with a ZIF-8 shell and loaded with cresyl violet, a fluorescent cytotoxic probe. The particles were stabilized with a fluorescein-functionalized amphiphilic polymer that improves colloidal stability, prevents unspecific sustained release, and protects the ZIF-8 shell from premature degradation, enabling efficient intracellular uptake in pancreatic cancer cells and cancer-associated fibroblasts. This study conducted a direct comparison between high-frequency alternating (AMF) or low-frequency rotating (RMF) magnetic fields inducing respectively nanoscale heating or mechanical actuation in a single magnetic MOF system. Both stimuli triggered significant cargo release and reduced cell viability in 2D cell cultures and 3D tumoral heterospheroids. These results strongly highlight the potential of MOF-based advanced drug delivery nanosystems responsive to dual-mode magnetic actuation strategy, paving the way for further evaluation in in vivo models to establish its translational relevance.