Nanoparticles Simultaneously Track as Many as 10 Different Optical Tags in Living Animal

Using nanoparticles designed specifically to produce a bright Raman spectroscopic signal, a team of investigators at the Center for Cancer Nanotechnology Excellence Focused on Therapy Response (Stanford University Center for Cancer Nanotechnology Excellence [CCNE]) has shown that it can simultaneously track as many as 10 different optical tags in a living animal. This work, the first to use surface-enhanced Raman spectroscopy (SERS) for multiplexed imaging in a living animal, was reported in the Proceedings of the National Academy of Sciences of the United States of America. The results point to the potential of Raman spectroscopy for multiplexed imaging of cancer biomarkers.

Sanjiv Sam Gambhir, M.D., Ph.D., principal investigator of the Stanford CCNE, led the team of investigators that used a set of 10 different silica-coated gold nanoparticles to create the multiplexed in vivo imaging technique. Each of the SERS nanotags generates a unique Raman spectrum when irradiated with near-infrared light. Spectral analysis software can deconvolute, or sort out, the light that each nanotag emits as part of a mixture, yielding the concentration of each individual nanotag.

In one set of experiments, the investigators injected the nanotags individually into a mouse and demonstrated that they could create a map of each nanotag’s location in the body. Using the five brightest nanotags, the researchers then attempted multiplexed analysis, and, indeed, the processing software was able to quantify the concentrations of individual nanotags as they accumulated in the liver.

The investigators are now optimizing their Raman microscope to maximize the depth within the body at which they can accurately measure the Raman signal from their nanotags. The researchers note that the chemical nature of the nanotags should enable them to attach specific binding agents for detecting cancer biomarkers as they are discovered.

This work, which is detailed in the paper “Multiplexed imaging of surface-enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. Investigators from Oxonica Materials also participated in this study. An abstract is available at the journal’s Web site.