Rapid exit strategy for nanotubes
Toxicology and environment
March 4, 2008
Nanotube-based systems are potential drug delivery vehicles for cancer therapy but the carriers must not linger in organs or tissue. Researchers from Stanford University School of Medicine have shown how to promote the clearance of intravenously injected single-walled carbon nanotubes (SWNTs) by adjusting their surface chemistry [Liu et al., Proc. Natl. Acad. Sci. USA (2008) 105, 1410].
The team used Raman spectroscopy to follow the fate of SWNTs injected into mice. This method is more reliable than alternative tracking systems that rely on radiolabels or fluorescent tags, according to Hongjie Dai, who led the work.
“SWNTs exhibit strong resonance Raman signals. The method is label-free and has high fidelity. There is no worry about labels falling off the tubes,” he says.
The team examined the postinjection blood concentration of SWNTs with various polyethylene glycol (PEG) coatings and investigated the biodistribution of SWNTs in various organs and tissue of mice ex vivo over a period of three months.
The length and branching structure of the PEG chains appears to be critical to SWNTs behavior in vivo. Nanotubes with a long, highly branched PEG coating remain longest in the bloodstream, suggesting sufficient stability for targeted imaging or therapeutic applications.
SWNTs with this type of surface chemistry also show the lowest tendency to collect in the liver and spleen. Near-complete clearance from the main organs is achieved in around two months.
Raman spectroscopy of the intestine, feces, kidney, and bladder reveal
that clearance is mostly the result of biliary excretion, with just
a small percentage excreted in urine. Necroscopy, histology, and blood
chemistry studies show no toxic side effects for these coated SWNTs.
The combination of rapid excretion and minimal toxicity implies that
properly functionalized nanotubes could, indeed, be used for drug
delivery applications, says Dai. The researchers are now pursuing
this with well PEGlyated SWNTs.
The finding is likely apply to most nanomaterials, not just SWNTs,
note the authors.
Paula Gould