Toward single-walled carbon nanotube-gadolinium complex as advanced MRI contrast agents: pharmacodynamics and global genomic response in small animals.

Abstract

Gadolinium nanoparticle-catalyzed single-walled carbon nanotubes (Gd-SWCNTs) have recently shown potential in vitro as high-performance T1 magnetic resonance imaging (MRI) contrast agents (CAs). Their preclinical safety assessment at nontoxic dosages is essential for MRI applications. Herein, the in vivo (in rats) pharmacodynamics of Gd-SWCNTs (water solubilized with the amphiphilic polymer PEG-DSPE) at the organ, tissue, molecular, and genetic level is reported. Gd-SWCNT, commercially available iron catalyzed SWCNTs (Fe-SWCNTs, control 1) and PEG-DSPE (control 2) solutions were intravenously injected at a potential nontoxic therapeutic dose (0.5 mg/kg body weight, single bolus). Postinjection, bright-field optical microscopy showed their macroscale distribution in lung, liver, kidney, brain, and spleen up to 5 days. Raman and transmission electron microscopy (TEM) showed their presence at the nanoscale within hepatocytes. Their effects on the host organ tissue, molecular, and genetic level were analyzed after 1, 5, 10, 20, and 30 days by histology, biomolecular [lipid peroxidation, plasma tumor necrosis factor TNF-α assay, microarrays] assays. The results indicate that Gd-SWCNTs neither cause any inflammation, nor damage to the above organs, nor any significant change in the lipid peroxidation or plasma proinflammatory cytokine (TNF-α) levels for all the groups at all time points. Global gene expression profile of liver (main organ for the metabolism) after day 1 treatment with Gd-SWCNTs shows that the gene regulation is directed toward maintaining normal homeostasis. The results taken together indicate that PEG-DSPE water-solubilized Gd-SWCNTs at potentially nontoxic dosages have pharmacodynamics similar to other commercially available Fe-SWCNTs and are suitable for future preclinical development as in vivo MRI CAs.