Carbon Nanotubes Modulate Activity of Cytotoxic Compounds via a Trojan Horse Mechanism.

Abstract

Carbon nanotubes (CNTs) are an emerging drug delivery system, but their success is thwarted by potential toxicity concerns. In vitro and in vivo studies imply toxic potential of CNTs, but their potential to influence toxicity of coadministered compounds still remains elusive. Therefore, the present study was conducted to determine the effect of multiwalled CNTs (MWCNTs) on the toxicity of cytotoxic compounds in macrophage (RAW 264.7), lung epithelial (A549), and breast cancer (MCF-7) cell lines. The results suggest that hydrophilicity/lipophilicity of the compounds is a critical parameter. The correlation between log P and enhanced cytotoxic activity followed an inverted U-shaped curve and log P close to 1 exhibited the highest increase in cytotoxicity. Further, the increase in cytotoxicity of drug/MWCNT combinations was proportional to the degree of cellular uptake of MWCNTs. A mathematical model was developed and validated with a test set of compounds. These results suggest that MWCNTs act as a "Trojan horse" for increased intracellular delivery of drugs resulting in enhanced cytotoxic activity.