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The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice

Science Translational Medicine  20 Apr 2011:
Vol. 3, Issue 79, pp. 79ra33
DOI: 10.1126/scitranslmed.3001963

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Minimal Toxicity of Nanoparticles for Raman Imaging

Nanoparticles are just the right size to interact with molecules and cells. But how best to harness them as tools in the service of medicine? The authors of this paper have pursued one application: nanoparticles created to image specific cells and molecules from inside living animals—and eventually patients—via Raman spectroscopy, a method based on inelastic light scattering. Although the Raman effect is weak, a gold core inside the nanoparticles boosts the Raman signal enough so that it can be detected inside living tissue. To prepare the ground for use of these nanoparticles in imaging colorectal cancer in patients, Thakor et al. thoroughly tested their toxicity in mice. When introduced through the colon, these gold-core nanoparticles did not cross the gut lining into the body of the mice, a result that bodes well for their future as diagnostic and treatment vehicles for gut diseases.

The authors first followed the fate of the silica-gold nanoparticles after the intravenous injection of a high dose into mice. Although their intravenous injection did cause temporary inflammation and some apoptosis in the liver 24 hours later, the nanoparticles were taken up by macrophages in the liver and spleen and eventually cleared from the body through the reticulo-endothelial system. A comprehensive survey of the mice revealed no ill effects of the nanoparticles on their general health or behavior. Their ECGs, blood pressure and heart rate were normal, and a panel of measurements of blood cells and chemistry revealed no effect of the particles. When the authors administered the nanoparticles into the colon, through the rectum, there was minimal evidence that the particles even passed into the animals’ circulation. Even the limited reaction in the liver seen after intravenous administration was absent and the particles were cleared within 5 minutes. The silica-gold nanoparticle tested in this paper can be coated with specific targeting molecules; the addition of one of these—a heptapeptide—did not increase the toxicity after treatment via the colon.

These results set the stage for Raman spectroscopic imaging of these targeted, gold-core nanoparticles in diagnosis of colorectal cancer or other disease of hollow viscera. Attachment of premalignant cancer specific targeting groups to the particle would allow detection of early lesions with a endoscopic Raman probe, an approach that could be extended to other clinical situations.


  • Citation: A. S. Thakor, R. Luong, R. Paulmurugan, F. I. Lin, P. Kempen, C. Zavaleta, P. Chu, T. F. Massoud, R. Sinclair, S. S. Gambhir, The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice. Sci. Transl. Med. 3, 79ra33 (2011).