Dataset Information

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-? 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-?) 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.

SUBMITTER: Avti PK

PROVIDER: S-EPMC3844433 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Avti Pramod K PK Talukdar Yahfi Y Sirotkin Matvey V MV Shroyer Kenneth R KR Sitharaman Balaji B

Journal of biomedical materials research. Part B, Applied biomaterials 20130404 6

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 ...[more]

PMID: 23559429

Similar Datasets

Project description:Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 ?g/cm(2) single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 ?g/cm(2) SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure