| الوصف: |
The use of magnetic nanoparticles (mNPs) to induce local hyperthermia has been emerging in recent years as a promising cancer therapy, in both a stand-alone and combination treatment setting, including surgery radiation and chemotherapy. The mNP solution can be injected either directly into the tumor, or administered intravenously. Studies have shown that some cancer cells associate with, internalize, and aggregate mNPs more preferentially than normal cells, with and without antibody targeting. Once the mNPs are delivered inside the cells, a low frequency (30-300kHz) alternating electromagnetic field is used to activate the mNPs. The nanoparticles absorb the applied field and provide localized heat generation at nano-micron scales. Treatment planning models have been shown to improve treatment efficacy in radiation therapy by limiting normal tissue damage while maximizing dose to the tumor. To date, there does not exist a clinical treatment planning model for magnetic nanoparticle hyperthermia which is robust, validated, and commercially available. The focus of this research is on the development and experimental validation of a treatment planning model, consisting of a coupled electromagnetic and thermal model that predicts dynamic thermal distributions during treatment. When allowed to incubate, the mNPs are often sequestered by cancer cells and packed into endosomes. The proximity of the mNPs has a strong influence on their ability to heat due to interparticle magnetic interaction effects. A model of mNP heating which takes into account the effects of magnetic interaction was developed, and validated against experimental data. An animal study in mice was conducted to determine the effects of mNP solution injection duration and PEGylation on macroscale mNP distribution within the tumor, in order to further inform the treatment planning model and future experimental technique. In clinical applications, a critical limiting factor for the maximum applied field is the heating caused by eddy currents, which are induced in the noncancerous tissue. Phantom studies were conducted to validate the ability of the model to accurately predict eddy current heating in the case of zero blood perfusion, and preliminary data was collected to show the validity of the model in live mice to incorporate blood perfusion. |
