Metal-organic framework-coated magnetite nanoparticles for synergistic magnetic hyperthermia and chemotherapy with pH-triggered drug release

In nanoplatform-based tumor treatment, combining chemotherapy with hyperthermia therapy is an interesting strategy to achieve enhanced therapeutic efficacy with low dose of delivery drugs. Compared to photothermal therapy, magnetic hyperthermia has few restrictions on penetrating tissue by an alternating magnetic field, and thereby could cure various solid tumors, even deep-tissue ones. In this work, we proposed to construct magnetic nanocomposites (Fe₃O₄@PDA@ZIF-90) by the external growth of metal-organic framework ZIF-90 on polydopamine (PDA)-coated Fe₃O₄ nanoparticles for synergistic magnetic hyperthermia and chemotherapy. In such multifunctional platform, Fe₃O₄ nanoparticle was utilized as a magnetic heating seed, PDA layer acted as an inducer for the growth of ZIF-90 shell and porous ZIF-90 shell served as drug nanocarrier to load doxorubicin (DOX). The well-defined Fe₃O₄@PDA@ZIF-90 core-shell nanoparticles were displayed with an average size of ca. 200 nm and possessed the abilities to load high capacity of DOX as well as trigger drug release in a pH-responsive way. Furthermore, the Fe₃O₄@PDA@ZIF-90 nanoparticles can raise the local temperature to meet hyperthermia condition under an alternating magnetic field owing to the magnetocaloric effect of Fe₃O₄ cores. In the <i>in vitro</i> experiments, the Fe₃O₄@PDA@ZIF-90 nanoparticles showed a negligible cytotoxicity to Hela cells. More significantly, after cellular internalization, the DOX-loaded Fe₃O₄@PDA@ZIF-90 nanoparticles exhibited distinctively synergistic effect to kill tumor cells with higher efficacy compared to chemotherapy or magnetic hyperthermia alone, presenting a great potential for efficient tumor therapy.