Magnetic nanoparticle hyperthermia cancer treatment efficacy dependence on cellular and tissue level particle concentration and particle heating properties

Abstract

The use of nanotechnology for the treatment of cancer affords the possibility of highly specific tumor targeting and improved treatment efficacy. Iron oxide magnetic nanoparticles (IONPs) have demonstrated success as an ablative mono-therapy and targetable adjuvant therapy. However, the relative therapeutic value of intracellular vs. extracellular IONPs remains unclear. Our research demonstrates that both extracellular and intracellular IONPs generate cytotoxicity when excited by an alternating magnetic field (AMF). While killing individual cells via intracellular IONP heating is an attractive goal, theoretical models and experimental results suggest that this may not be possible due to limitations of cell volume, applied AMF, IONP concentration and specific absorption rate (SAR). The goal of this study was to examine the importance of tumor size (cell number) with respect to IONP concentration. Mouse mammary adenocarcinoma cells were incubated with IONPs, washed, spun into different pellet sizes (0.1, 0.5 and 2 million cells) and exposed to AMF. The level of heating and associated cytotoxicity depended primarily on the number of IONPs /amount Fe per cell pellet volume and the relative volume of the cell pellet. Specifically, larger cell pellets achieved greater relative cytotoxicity due to greater iron amounts, close association and subsequently higher temperatures.

Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study

“…In recent years, nanoparticle hyperthermia has been demonstrated to enhance wave energy absorption (laser photothermal therapy and ultrasound) and to confine energy generation (magnetic nanoparticle hyperthermia) in tumors to minimize collateral tissue damage. In magnetic nanoparticle hyperthermia, magnetic nanoparticles delivered to the tumor site can generate heat when subject to an alternating magnetic field [1][2][3][4][5]. Once the nanoparticles are manufactured, the induced volumetric heat generation rate subject to a specific magnetic field and thermal dosage required to damage the tumor are primarily dependent on the concentration distribution of nanoparticles in the tumor.…”