Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy

Superparamagnetic iron oxide nanoparticles (SPIONs) havebeen widelyemployed in biomedical fields, including targeted delivery of antitumortherapy. Conventional magnetic tumor targeting has used simple staticmagnetic fields (SMFs), which cause SPIONs to linearly aggregate intoa long chain-like shape. Such agglomeration greatly hinders the intracellulartargeting of SPIONs into tumors, thus reducing the therapeutic efficacy.In this study, we investigated the enhancement of the intracellularuptake of SPIONs through the application of rotating magnetic fields(RMFs). Based on the physical principles of SPION chain disassembly,we investigated physical parameters to predict the chain length favorablefor intracellular uptake. Our prediction was validated by clear visualizationof the intracellular distributions of SPIONs in tumor cells at bothcellular and three-dimensional microtissue levels.To identify the potential therapeutic effects of enhanced intracellularuptake, magnetic hyperthermia as antitumor therapy was investigatedunder varying conditions of magnetic hyperthermia and RMFs. The resultsshowed that enhanced intracellular uptake reduced magnetic hyperthermiatime and strength as well as particle concentration. The proposedmethod will be useful in the development of techniques to determinethe optimized physical conditions for the enhanced intracellular uptakeof SPIONs in antitumor therapy.