Seeded-Growth of ZIF-8 onto Magnetic Nanoparticles: Smart Nanocarriers with Ultrahigh Drug Loading for AMF-Triggered Release.

A seeded growth strategy was developed to synthesize core-shell magnetic metal-organic framework (MOF) composites for magnetic hyperthermia (MHT) and MHT-triggered drug delivery. Cubic or spherical iron oxide nanoparticles, with nanocubes selected for their superior MHT performance, were coated with cetyltrimethylammonium bromide to enable aqueous ZIF-8 shell growth. Shell thickness strongly influenced heating efficiency under alternating magnetic fields (AMFs), with thinner shells and cubic cores yielding enhanced MHT performance. Doxorubicin (Doxo) was used as a model chemotherapeutic drug and loaded either by surface adsorption or via in-situ encapsulation during ZIF-8 growth, the latter achieving an exceptional loading efficiency of 98%. To ensure stability in physiological environments, an amphiphilic polymer coating was applied, improving dispersion while regulating shell degradation and drug release. Doxo-loaded composites exhibited efficient cellular uptake and lysosomal localization in glioblastoma and breast cancer cells. Confocal microscopy revealed that magnetic field exposure induced lysosomal permeabilization and redistribution of Doxo, indicating a potential lysosomal escape mechanism. Notably, enhanced cytotoxicity occurred only when AMFs were applied to Doxo-loaded composites, despite no measurable bulk temperature increase, suggesting localized MHT-induced intracellular damage. Overall, shell-tunable magnetic-MOF nanohybrids emerge as promising platforms for controlled, heat-free intracellular drug activation for targeted cancer therapy.