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

ABSTRACT

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.