Document Type and Release Option
Thesis (open access)
Dr. Eric Gato
Serious side effects and treatment resistance are the main impediments to successful cancer therapy. A variety of nanoparticles have been used for localized, site-specific treatment that prevent or circumvent these impediments. Microwaves alone have been previously used for thermal ablation of various tumors, setting precedence for their successful use in live organisms. In cell culture studies, it has been observed that multiwall carbon nanotubes (MWCNTs) instantly and efficiently absorb microwaves, causing hyperthermia of cells in direct contact with them with unnoticed harm to other cells. It is hypothesized that a treatment can be developed based on a safe microwave heating schedule for the selective ablation of tumor cells in vivo using MWCNT-ab conjugates as a targeting medium and mice as animal models. This was accomplished by conjugating MWCNTs with anti-PSMA antibodies (ab) in order to induce the selective uptake of MWCNTs by PC3 cells, known to significantly over-express PSMA antigens in comparison to non-cancerous cells. This study sought to elucidate any toxicological effects by the characterization of MWCNT-ab distribution, clearance, and toxicology in mice following microwave hyperthermia. This was assessed through clinical chemistry and analyzing gene expression in the brain, liver, and kidney. Results seem to suggest that exposure to MWCNT-Ab cause injury to the liver and kidney in higher doses. Blood serum markers of AST and creatinine were significantly elevated in some of the treatment groups. Similarly, upregulation of IL6, NFkB, PTGS2, and TNF-α in brain, liver and kidney tissues was observed for some of the MWCNT-Ab exposed mice. The results are consistent with our initial assessment that MWCNT-Ab are safe at low doses and display increasing toxicity as the concentration of MWCNTs increase. In conclusion, exposure to MWCNT conjugated antibody and microwave may produce inflammatory response in the brain, liver and kidney of mice.
Mixson, Andrew C., "Assessment of the toxicological effects of CNT-Ab in mice followed by microwave hyperthermia 14 days post treatment." (2020). Honors College Theses. 477.