title: Iron oxide nanoparticle hyperthermia and chemotherapy cancer treatment.
abstract: The benefit of combining hyperthermia and chemotherapy to treat cancer is well established. However, combined therapy has not yet achieved standard of care status. The reasons are numerous and varied, however the lack of significantly greater tumor cell sensitivity to heat (as compared to normal cells) and the inability to deliver heat to the tumor in a precise manner have been major factors. Iron oxide nanoparticle (IONP) hyperthermia, alone and combined with other modalities, offers a new direction in hyperthermia cancer therapy via improved tumor targeting and an improved therapeutic ratio. Our preliminary studies have demonstrated tumor cell cytotoxicity (in vitroandin vivo) with IONP heat and cisplatinum (CDDP) doses lower than those necessary when using conventional heating techniques or cisplatinum alone. Ongoing studies suggest such treatment could be further improved through the use of targeted nanoparticles.
  
  
  METHODS
  In vivo:IONPs (5mg of iron per gram of tumor) were administered into MTG-B flank tumors in female C3H-HEJ mice directly after cisplatinum chemotherapy (0.1ml/kg of body mass) was intraperitoneally injected. An 160 KHz, 350-450 Oe AMF (alternating magnetic field) was used to induce particle heating.In vitro:Mouse mammary adenocarcinoma cells (MTG-B) cells were grown and exposed to IONP hyperthermia and cisplatinum. IONPs not associated with cells were removed by washing prior to heat induction by an AMF field. Acute cell survival, via trypan blue assay, was used to quantify the level of cytotoxicity.
  
  
  RESULTS
  In vitrostudies, using IONP + cisplatinum, have demonstrated promising cytotoxicity enhancement. Ongoing studies are being pursued to further define the mechanism of action, temporal associations and pathophysiology of combined IONP hyperthermia and chemotherapy treatment. Preliminaryin vivoIONP /cisplatinum studies have shown a tumor growth delay/volume reduction greater than either modality alone at comparable doses. Further enhancement of this treatment success appears to depend on a better understanding of IONP dose and tumor cell association, chemotherapy dose and administration technique, the spatial and temporal treatment relationship of the two modalities and optimal AMF - IONP coupling.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Aa
authors.initials: A
authors.lastname: Petryk
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA ; Dartmouth Medical School, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Aj
authors.initials: A
authors.lastname: Giustini
authors.affiliation: Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115 USA.
authors.forename: P
authors.initials: P
authors.lastname: Ryan
authors.affiliation: Dartmouth Medical School, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Rr
authors.initials: R
authors.lastname: Strawbridge
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA ; Dartmouth Medical School, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Pj
authors.initials: P
authors.lastname: Hoopes
keywords: AMF; HT-29; Iron oxide; MTG-B; chemotherapy; cisplatinum; murine; nanoparticle