Ablation of cells in mice using antibody-functionalized multiwalled carbon nanotubes (Ab-MWCNTs) in combination with microwaves

Abstract

This is a proof-of-principle study on the combination of microwaves and multiwalled carbon nanotubes to induce in vivo, localized hyperthermic ablation of cells as a potential methodology for the treatment of localized tumors. Compared to conventional methods, the proposed approach can create higher temperatures in a rapid and localized fashion, under low radiation levels, eliminating some of the unwanted side effects. Following successful ablation of cancer cells in cell culture and zebrafish tumor-xenograft models, it is hypothesized that a cancer treatment can be developed using safe microwave irradiation for selective ablation of tumor cells in vivo using carbon nanotube-Antibody (CNT-Ab) conjugates as a targeting agent. In this study, mice were used as an animal model for the optimization of the proposed microwave treatment strategy. The safe dose of CNT-Ab and microwave radiation levels for mice were determined. Further, CNT-Ab distribution and toxicology in mice were qualitatively determined for a time span of two weeks following microwave hyperthermia. The results indicate no toxicity associated with the CNT-Ab in the absence of microwaves. CNTs are only found in the proximity of the site of injection and have been shown to effectively cause hyperthermia induced necrosis upon exposure to microwaves with no noticeable damage to other tissues that are not in direct contact with the CNT-Ab. To understand the cellular immune response towards CNT-Abs, transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to assay for their ability to phagocytize CNT-Ab. Our results indicate that macrophages and neutrophils were able to actively phagocytose CNT-Abs shortly after injection. Taken together, this is the first study to show that CNTs can be used in combination with microwaves to cause targeted ablation of cells in mice without any side effects, which would be ideal for cancer therapies.