Using kinetic Monte Carlo simulations to design efficient magnetic nanoparticles for clinical hyperthermia.

Abstract

The purpose of this study was to identify the properties of magnetite nanoparticles that deliver optimal heating efficiency, predict the geometrical characteristics to get these target properties, and determine the concentrations of nanoparticles required to optimize thermotherapy. Kinetic Monte Carlo simulations were employed to identify the properties of magnetic nanoparticles that deliver high Specific Absorption Rate (SAR) values. Optimal volumes were determined for anisotropies ranging between 11 and 40kJ/m3 under clinically relevant magnetic field conditions. Atomistic spin simulations were employed to determine the aspect ratios of ellipsoidal magnetite nanoparticles that deliver the target properties. A numerical model was developed using the extended cardiac-torso (XCAT) phantom to simulate low-field (4 kA/m) and high-field (18 kA/m) prostate cancer thermotherapy. A stationary optimization study exploiting the Method of Moving Asymptotes (MMA) was carried out to calculate the concentration fields that deliver homogenous temperature distributions within target thermotherapy range constrained by the optimization objective function. A time-dependent study was used to compute the thermal dose of a 30-min session. Prolate ellipsoidal magnetite nanoparticles with a volume of 3922 ± 35 nm3 and aspect ratio of 1.56, which yields an effective anisotropy of 20kJ/m3 , constituted the optimal design at current maximum clinical field properties (H0 =18 kA/m, f=100kHz), with SAR=342.0 ± 2.7 W/g, while nanoparticles with a volume of 4147 ± 36 nm3 , aspect ratio of 1.29, and effective anisotropy 11kJ/m3 were optimal for low-field applications (H0 =4 kA/m, f=100kHz), with SAR=50.2 ± 0.5 W/g. The average concentration of 3.86 ± 0.10 and 0.57 ± 0.01mg/cm3 at 4 and 18 kA/m, respectively, were sufficient to reach therapeutic temperatures of 42-44°C throughout the prostate volume. The thermal dose delivered during a 30-min session exceeded 5.8 Cumulative Equivalent Minutes at 43°C within 90% of the prostate volume (CEM43T90 ). The optimal properties and design specifications of magnetite nanoparticles vary with magnetic field properties. Application-specific magnetic nanoparticles or nanoparticles that are optimized at low fields are indicated for optimal thermal dose delivery at low concentrations.