Preclinical evaluation of PEG-Multiwalled carbon nanotubes: Radiolabeling, biodistribution and toxicity in mice

Multiwalled carbon nanotubes (MWCNTs) have been integrated into many recent biomedical studies since their cylindrical architecture, high aspect ratio, and specific functionalization could allow carbon nanotubes (CNTs) to penetrate into the cells through the plasma membrane. However, one of the main challenges in the in vivo applications of these nanoparticles is their reduced biocompatibility and poor dispersibility. Furthermore, even today, there are still some knowledge gaps concerning CNTs toxicity and their behavior considering in vivo tumor-bearing mice models. In this sense, herein, polyethylene glycol chains were covalently bound to MWCNTs (PEG-MWCNTs) through an aliphatic nucleophilic substitution chemical reaction and radiolabeled with [99 mTc]Tc, yielding a high radiochemical rate. The physicochemical characterization procedures showed that the PEG chains were successfully covalently attached to the MWCNT surface. Biodistribution studies were carried out in tumor-bearing mice, and the results revealed that a produced system displays prolonged blood circulation time and relevant tumor uptake rates. Toxicological data were obtained from testing on healthy animals, and the data obtained revealed that PEG-MWCNTs did not induce an important toxicity profile. Considering all the results obtained in this work, the PEG-coated MWCNTs can be considered a potential candidate for future oncologic applications.