Investigating the toxicology of intramuscular injected multiwalled carbon nanotubes conjugated antibody (CNT-Ab) in mice followed by microwave hyperthermia

摘要

Carbon nanotubes bound to tumor specific antibodies offer specific treatment for cancer cells without affecting surrounding tissue. The present study seeks to affirm the initial results of CNTs in cancer therapy by investigating the toxicological effect in mice injected with CNT-Ab followed by microwave hypothermia. We were particularly interested in evaluating the biodistribution, toxicity, and immune response that may be elicited from CNT-Ab exposure in mice. 4–5 week old mice (C57BL/6) were injected with various concentrations and combinations of multiwalled carbon nanotubes (MWCNT) conjugated with specific prostate-specific membrane antigen (PMSA) antibodies. After 1-week post-injection, mice were sacrificed followed by the collection of blood separated into serum, liver, kidney and other tissues for further analysis. Serum total protein concentration across the treatment groups was varied. No significant changes in albumin levels were detected when compared to the control group (No Treatment). Group YE (.125 mg/ml anti-PSMA-MWCNT + Microwave) was found to have consistently high blood serum analyte levels, indicating impaired liver and kidney function. Likewise, groups YB (Microwave only), YF [.5 mg/ml anti-PSMA-MWCNT (No Microwave)], and YG (.5 mg/ml plain MWCNT + Microwave) seemed to show indications of impaired liver function. Analysis of gene expression revealed a significant impact on the NF-KB inflammatory response pathway. NF-KB gene was up-regulated relative to controls in all treatment groups. These results seem to suggest marginal toxicity from the injection of CNT-Ab followed by microwave hyperthermia in mice subjects.