Multilayered inorganic-organic microdisks as ideal carriers for high magnetothermal actuation: assembling ferrimagnetic nanoparticles devoid of dipolar interactions

The two major limitations for nanoparticle based magnetic hyperthermia in theranostics are the delivery of a sufficient number of magnetic nanoparticles (MNPs) with high heating power to specific target cells and the residence time of the MNPs at the target location. Ferromagnetic or Ferrimagnetic single domain nanoparticles (F-MNPs), with a permanent magnetic dipole, produce larger magnetic and thermal responses than superparamagnetic nanoparticles (SP-MNPs) but also agglomerate more. MNP agglomeration degrades their heating potential due to dipolar interaction effects and interferes with specific targeting. Additionally, MNPs bound to cells are often endocytosed by the cells or, in vivo, cleared out by the immune system via uptake in macrophages. Here, we present a versatile approach to engineer inorganic-polymeric microdisks, loaded with biomolecules, fluorophores and Fe3O4 F-MNPs that solves both challenges. These microdisks deliver the F-MNPs efficiently, while controlling any undesirable agglomeration and dipolar interaction, while also rendering the F-MNPs endocytosis resistant. We show that these micro-devices are suitable carriers to transport a flat assembly of F-MNPs to the cell membrane unchanged, preserving the magnetic response of the MNPs in any biological environment. The F-MNPs concentration per microdisk and degree of MNP interaction are tunable. We demonstrate that the local heat generated in microdisks is proportional to the surface density of F-MNPs when attached to the cell membrane. The key innovation in the production of these microdisks is the fabrication of a mushroom-shaped photolithographic template that enables easy assembly of the inorganic film, polymeric multilayers, and MNP cargo while permitting highly efficient lift-off of the completed microdisks. During the harvesting of the flat microdisks, the supporting mushroom-shaped templates are sacrificed. These resulting magnetic hybrid microdisks are tunable and efficient devices for magnetothermal actuation and hyperthermia.