Hyperthermia Using Antibody-Conjugated Magnetic Nanoparticles and Its Enhanced Effect with Cryptotanshinone

Heat dissipation by magnetic nanoparticles (MNPs) under an alternating magnetic field can be used to selectively treat cancer tissues. Antibodies conjugated to MNPs can enhance the therapeutic effects of hyperthermia by altering antibody-antigen interactions. Fe3O4 nanoparticles (primary diameter, 20-30 nm) coated with polyethylenimine (PEI) were prepared and conjugated with CH11, an anti-Fas monoclonal antibody. HeLa cell growth was then evaluated as a function of antibody and MNP/antibody complex doses. HeLa cell growth decreased with increased doses of the antibody and complexes. However, MNPs alone did not affect cell growth; thus, only the antibody affected cell growth. In hyperthermia experiments conducted using an alternating magnetic field frequency of 210 kHz, cell viability varied with the intensity of the applied alternating magnetic field, because the temperature increase of the culture medium with added complexes was dependent on magnetic field intensity. The HeLa cell death rate with added complexes was significantly greater as compared with that with MNPs alone. Cryptotanshinone, an anti-apoptotic factor blocker, was also added to cell cultures, which provided an additional anti-cancer cell effect. Thus, an anti-cancer cell effect using a combination of magnetic hyperthermia, an anti-Fas antibody and cryptotanshinone was established.