Design consideration for surface-enhanced (resonance) raman scattering nanotag cores

Surface-enhanced (resonance) Raman spectroscopy (SE(R)RS) holds great promise for the in vivo detection of multiple disease markers. Nanotags consisting of a metallic nanoparticle decorated with reporter molecules encapsulated in either an inert or biofunctionalized shell, for inactive or active targeting, have been developed. To improve the tissue depth from which the signal can be detected, it is preferable to operate with excitation in the near-infrared wavelengths; however, this reduces the inherent Raman signal intensity. The signal strength can be reestablished by matching the absorbance of the nanoparticle with the laser excitation. However, nanopartides must get physically larger to support absorbances in the near-infrared region, which can have an adverse affect on cellular uptake. In this paper we compare the use of silver nanoparticles with plasmon absorbances at longer wavelengths with clusters (2-4 nanopartides) formed from much smaller nanoparticles which support so-called "hot spots". We find that the small clusters outperform the resonant single nanoparticles with respect to the observed SE(R)RS signal. It has also previously been shown in the literature that small nanoparticles are more readily taken up into cells than larger nanoparticles. This knowledge combined with the results reported here highlight an important design consideration in that new SE(R)RS active nanotags should be made from coupled small dimensional nanoparticles rather than large single nanoparticles that support absorbances in the near-infrared region