A novel strategy combining magnetic particle hyperthermia pulses with enhanced performance binary ferrite carriers for effective in vitro manipulation of primary human osteogenic sarcoma cells

The present study examines the heating efficiency of a combination of manganese or cobalt ferrites in a binary (Co- or Mn-) ferrite nanoparticle form with magnetite, covered with citric acid to improve biocompatibility. The nanoparticle synthesis is based on the aqueous co-precipitation of proper salts, a facile, low-cost, environmentally friendly and high yield synthetic approach. By detailed structural and magnetic characterisation, the direct influence of structural and magnetic features on magnetic hyperthermia concludes to optimum heating efficiency. At a second stage, best performing magnetic nanoparticles undergo in vitro testing in three cell lines: one cancer cell line and two reference healthy cell lines. Both binary ferrite (MnFe2O4/Fe3O4 and CoFe2O4/Fe3O4) appear to be internalised and well tolerated by the cells while a versatile hyperthermia protocol is attempted in an effort to further improve their in vitro performance. Within this protocol, hyperthermia sequences are split in two runs with an intermediate 48 h time interval cell incubation stage while in each run a variable field mode (single or multiple pulses) is applied. Single-pulse field mode represents a typical hyperthermia application scheme where cells undergo the thermal shock continuously. On the other hand multiple-pulses mode refers to multiple, much shorter in duration AC field changes (field ON/OFFs), at each hyperthermia run, resulting eventually in high heating rate and much more harmful cell treatment. Consequently, we propose a novel series of improved performance heat mediators based on ferrite structures which show maximum efficiency at cancer cells when combined with a versatile multiple-pulse hyperthermia module.