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.

Stabilization of Carbon Nanotubes and Graphene by Tween-80: Mechanistic Insights from Spectroscopic and Simulation Studies

“…Ltd., India. The size characteristics were confirmed by high resolution transmission electron microscopy, and impurities were quantified by thermogravimetry; the characterization of these CNPs is described in earlier reports from our group. , …”

“…A stock solution of CNPs was prepared in water or deuterated water by probe sonication as described earlier. , Briefly, 10 mg of CNP powder was added into an aqueous solution of 10 mg/mL of Tween-80 (prepared in water or deuterated water) and sonicated for 5 min. The stock suspension was appropriately diluted with 10 mg/mL of Tween-80 solution (prepared in water or deuterated water) to obtain the desired concentrations of CNPs, and spectra were recorded within 1 h of sample preparation.…”

“…On the other hand, polyethoxylates stabilize suspensions at relatively lower concentrations, typically below 10 mg/mL. − Furthermore, polyethoxylates also exhibit good biocompatibility and are a common constituent in pharmaceutical and cosmetic products. This also makes them a good candidate for dispersing NPs for toxicological evaluations and biomedical applications. ,,− …”

“…Polyoxyethylene sorbitan monooleate, commonly known as Tween-80, is one of the most commonly employed polyethoxylate surfactants. ,,, Despite its frequent use in dispersing NPs, the mechanism of stabilization by this surfactant has been poorly studied. Microscopic examination of multi-walled CNTs (MWCNTs) revealed complete and uniform coverage of the CNT surface with Tween-80 molecules .…”

Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes

“…At studying the effect of MWCNTs on the toxicity of cytotoxic compounds in macrophage (RAW 264.7), lung epithelial (A549), and breast cancer (MCF-7) cell lines, it was found that hydrophilicity/lipophilicity of the compounds was determinant. The dependence of log P vs. cytotoxic activity showed a quasi-parabolic course, the highest value being observed at log P close to 1 and the degree of cellular uptake of MWCNTs affected the cytotoxicity of drug/MWCNT combinations, suggesting that MWCNTs function as a "Trojan horse", ensuring improved intracellular delivery of drugs leading to increased cytotoxic activity [274]. Nahle et al [275] compared in vitro responses of rat alveolar NR8383 cells to pristine, anionic, and cationic MWCNTs using cytotoxicity assays, transcriptomics, and proteomics.…”