Quantitative evaluation of effects of coupled temperature elevation, thermal damage, and enlarged porosity on nanoparticle migration in tumors during magnetic nanoparticle hyperthermia

摘要

Using simulation to accurately design a heating protocol in magnetic nanoparticle hyperthermia relies on not only the initial nanoparticle distribution, but also the dynamic particle migration during heating. A coupled theoretical framework consisting of nanoparticle migration in a porous medium model and temperature elevation in a heat transfer model was developed to evaluate possible nanoparticle redistribution during local heating. Five generated tumor models from microcomputed tomography (microCT) with nanoparticle deposition were used to predict temperature elevations and assess local thermal damage when each tumor was subject to an alternating magnetic field. Local thermal damage further changed the interstitial structure in the tumor, resulting in enhancements in porosity and diffusion coefficient to promote nanoparticle diffusion to low concentration regions. The distribution volumes of nanoparticles in the highest concentration range reduced after heating, while those in the lower concentration ranges increased. After heating, the total nanoparticle distribution volume defined as the tumor volume occupied by nanoparticles was 21% bigger than that before the heating. The theoretical predictions of nanoparticle migration trend agree well with experimental results of microCT scan analyses. It is concluded that thermal damage induced enhancement in nanoparticle diffusion may be one of the mechanisms to explain nanoparticle migration during magnetic nanoparticle hyperthermia. Results from this study may suggest a feasibility of enhancing nanoparticle dispersion from injection sites using deliberate thermal damage.