Hyperthermia, as an independent modality or in combination with standard cancer treatments such as
chemotherapy and radiation, has been established in vitro and in vivo as an effective cancer treatment.
However, despite efforts over the past 25 years, such therapies have never been optimized or widelyaccepted
clinically. Although methods continue to improve,
conventionally-delivered heat (RF, ultrasound,
microwave etc) can not be delivered in a tumor selective manner. The development of antibody-targeted, or
even nontargeted, biocompatible iron oxide nanoparticles (IONP) now allows delivery of cytotoxic heat to
individual cancer cells. Using a murine mouse mammary adenocarcinoma (MTGB) and human colon
carcinoma (HT29) cells, we studied the biology and treatment of IONP hyperthermia tumor treatment.
Methods: Cancer cells (1 x 106) with or without iron oxide nanoparticles (IONP) were studied in culture or
in vivo via implanted subcutaneously in female C3H mice, Tumors were grown to a treatment size of 150
mm3 and tumors volumes were measured using standard 3-D caliper measurement techniques. Mouse
tumors were heated via delivery of an alternating magnetic field, which activated the nanoparticles, using a
cooled 36 mm diameter square copper tube induction coil which provided optimal heating in 1.5 cm wide
region of the coil. The IONPs were dextran coated and had a hydrodynamic radius of approximately 100
nm. For the in vivo studies, intra-tumor, peritumor and rectal (core body) temperatures were continually
measured throughout the treatment period. Results: Although some eddy current heating was generated in
non-target tissues at the higher field strengths, our preliminary IONP hyperthermia studies show that whole
mouse AMF exposure @160 KHz and 400 or 550 Oe, for a 20 minutes (heat-up and protocol heating),
provides a safe and efficacious tumor treatment. Initial electron and light microscopic studies (in vitro and
in vivo) showed the 100 nm used in our studies are rapidly taken up and retained by the tumor cells.
Additional in vitro studies suggest antibodies can significantly enhance the cellular uptake of IONPs.