Optimizing and characterizing fundamentals of magnetic heating in iron oxide nanoparticles for use in cancer hyperthermia therapy

Abstract

Iron oxide magnetic nanoparticles generate heat upon application of high frequency magnetic field that can be harnessed to treat cancer by achieving a temperature rise of > 43 °C. This study investigates and optimizes parameters such as magnetic field strength and frequency, solution viscosity, nanoparticle size, composition, and magnetic properties to maximize the heat generation in iron oxide magnetic nanoparticles (MNPs). Data were normalized to calculate SAR (specific absorption rate, W/g Fe) to determine the most effective parameters for magnetic heating, resulting in values as high as 1001 W/g Fe for the MNPs. Calculations based on the linear response theory and the Stoner-Wohlfarth theory were used to estimate nanoparticle SAR, and yielded results in agreement with the experiments. Efforts were made to determine nano-scale temperatures in the core of polymeric micelles, which are imbedded with a temperature sensitive fluorescent dye and magnetic nanoparticles. Experimental and computational macro-scale tumor models were investigated to observe the bulk temperature rise (>43 °C), and determine the applicability of the MNPs investigated for magnetic hyperthermia. It was determined that although there was minimal local temperature rise in the core of magnetic micelles, a temperature rise sufficient to reach hyperthermia conditions was observed in bulk tumor models measuring at least 0.8 mm in diameter. Additionally, bulk heating of Chinese Hamster Ovary (CHO) cells using MNPs demonstrated that hyperthermia led to cell death in the temperature range of 43 °C to 46 °C, while causing minimal toxicity concerns. A separate investigation (Chapter 9) was undertaken to validate single-use cell culture bags by developing a methodology to measure the toxicity caused by a leachate found to release from these bags, which are finding greater acceptance in the biopharmaceutical industry. CHO cells were used to investigate the dependence of leachate toxicity on cell culture type, mixing, culture volume, and the duration of cell exposure to the leachate. It was determined that the leachates posed a higher toxicity to suspended CHO-K1 cells compared to adherent cells, while use of constant mixing and long term exposure of cells to leachates led to considerable cell death.