In Vivo Behavior of Large Doses of Ultrashort and Full-Length Single-Walled Carbon Nanotubes after Oral and Intraperitoneal Administration to Swiss Mice

Abstract

Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length, and surface chemistry in Swiss mice. Transmission electron microscopy (TEM), Raman, near-infrared (NIR), and X-ray photoelectron spectroscopies have been used to characterize the tested materials. The dose of SWNT materials used in this study is considerably higher than that proposed for most biomedical applications, but it was deemed necessary to administer such large doses to accurately assess the toxicological impact of the materials. In an acute toxicity test, SWNTs were administered orally at a dose level of 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiberlike structures. When structure lengths exceeded 10 mum, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (<300 nm) well-individualized SWNTs can escape the reticuloendothelial system to be excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual "molecule-like" species.

Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes

“…delivery, and optical emission in NIR2 in a preclinical mouse model of ovarian cancer. Our acute toxicity studies are consistent with several other preliminary studies exploring the safety of M13 and SWNTs, in that a panel of serum biomarkers were not elevated (30)(31)(32)(33). Collectively, we believe these findings suggest that these materials warrant further consideration for clinical translation, which would include the development of instruments for real-time imaging, outcomes research such as survival studies in preclinical models, and rigorous safety evaluation through the National Characterization Laboratory (National Cancer Institute) and others to assess long-term trafficking and clearance of these materials as well as chronic toxicity studies.…”

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

“…Due to the range of parameters listed earlier which have been shown to affect CNTs toxicity, this is an area which will require the continual attention of toxicologists in the future. Using just one example, some evidence (Thurnherr et al, 2011) points to Fe (iron) impurities on CNTs at high concentrations increasing the observed cytotoxic response, while other research (Kolosnjaj-Tabi et al, 2010) claims the opposite. Clearly, much further study is required in this area before CNT technology can be applied to cancer treatment.…”

Biological Activities of Carbon Nanotubes

“…Absorption from GIT depends on the physiochemical properties of nanomaterials. For example, Kolosnjaj-Tabi et al (2010) reported that when SWCNT were administered orally (1000 mg/kg body weight), neither death nor growth or behavioral troubles were observed. However, intraperitoneal administration of SWCNT (50-1000 mg/kg body weight) can coalesce inside the body to form fiber-like structures.…”

“…When SWCNT length exceeded 10 m, they irremediably induced granuloma formation compared to smaller aggregates which did not induce granuloma but persisted inside the cells for up to 5 months post-administration. Individualized SWCNT (< 300 nm) can escape the reticuloendothelial system to be excreted through the kidney and bile ducts (Kolosnjaj-Tabi, Hartman et al 2010). Oral exposure of corn oil-suspended CNT induced oxidative and genotoxic changes in the lung and liver of rats (Folkmann, Risom et al 2009).…”