title: Kinetics and pathogenesis of intracellular magnetic nanoparticle cytotoxicity.
abstract: Magnetic nanoparticles excited by alternating magnetic fields (AMF) have demonstrated effective tumor-specific hyperthermia. This treatment is effective as a monotherapy as well as a therapeutic adjuvant to chemotherapy and radiation. Iron oxide nanoparticles have been shown, so far, to be non-toxic, as are the exciting AMF fields when used at moderate levels. Although higher levels of AMF can be more effective, depending on the type of iron oxide nanoparticles use, these higher field strengths and/or frequencies can induce normal tissue heating and toxicity. Thus, the use of nanoparticles exhibiting significant heating at low AMF strengths and frequencies is desirable. Our preliminary experiments have shown that the aggregation of magnetic nanoparticles within tumor cells improves their heating effect and cytotoxicity per nanoparticle. We have used transmission electron microscopy to track the endocytosis of nanoparticles into tumor cells (both breast adenocarcinoma (MTG-B) and acute monocytic leukemia (THP-1) cells). Our preliminary results suggest that nanoparticles internalized into tumor cells demonstrate greater cytotoxicity when excited with AMF than an equivalent heat dose from excited external nanoparticles or cells exposed to a hot water bath. We have also demonstrated that this increase in SAR caused by aggregation improves the cytotoxicity of nanoparticle hyperthermia therapyin vitro.
authors.affiliation: Dartmouth Medical School, 1 Rope Ferry Road, Hanover, NH, USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Giustini
authors.affiliation: Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Gottesman
authors.affiliation: Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: A A
authors.initials: AA
authors.lastname: Petryk
authors.affiliation: Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: A M
authors.initials: AM
authors.lastname: Rauwerdink
authors.affiliation: Dartmouth Medical School, 1 Rope Ferry Road, Hanover, NH, USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
keywords: AMF; Hyperthermia; SAR; intracellular hyperthermia; nanoparticle; specific absorption rate; tumor