Heating Induced Nanoparticle Redistribution in PC3 Tumors: In Vivo Experiments and MicroCT Imaging Analyses

Author/Creator

Author/Creator ORCID

Date

2019-01-01

Department

Mechanical Engineering

Program

Engineering, Mechanical

Citation of Original Publication

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Abstract

The focus of this dissertations research is to evaluate how intensive local heating or mild whole-body heating alters transport properties in tumors, therefore, leading to nanoparticle redistribution or enhanced delivery. The first project of the dissertations research is to perform an experimental study on tissue-equivalent phantom gels to visualize magnetic nanoparticle redistribution after the gel was heated via magnetic nanoparticle hyperthermia. 0.1cc magnetic nanoparticles was injected into agarose gels. After 15 minutes, magnetic nanoparticle heating altered nanoparticle distribution in the gel via pushing nanoparticles further away from the infusion site, resulting in a 26% increase in nanoparticle distribution volume. The second project is to conduct in vivo experiments to evaluate whether local heating of 25 minutes using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors, analyzed by microCT images of resected tumors. Nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high Hounsfield unit (HU) range (> 1.8*106 W/m3) is 10% smaller in the heating group, while in the low range of 0.6 - 1.8*106 W/m3, it is 95% larger in the heating group. The percentage in HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group. The third project is to perform in vivo experiments to assess whether mild whole-body heating affects nanoparticle delivery to PC3 tumors. The mice in the experimental group were subjected to whole body hyperthermia at 39-40�C for one hour. 0.2 cc of a newly developed gold nanoparticles (AuNPs) was delivered intravenously via the tail vein. Analyses of microCT scans of the resected tumors showed a 39% decrease in the IFP of PC3 tumors after whole body hyperthermia treatment, with a statistically significant reduction of 50% evident 2 hours post heating, and 58% reduction found 24 hours post heating; and it illustrated that nanoparticles were more concentrated near the tumor periphery than the tumor center. The mass index suggested overall 42% more nanoparticle delivery in the experimental group than that in the control group.