Abstract
The unique spectral signatures and biologically inert compositions of surface-enhanced resonance Raman scattering (SERRS) nanoparticles make them promising contrast agents for in vivo cancer imaging. Our SERRS nanoparticles consist of a 60-nm gold nanoparticle core that is encapsulated in a 15-nm-thick silica shell wherein the resonant Raman reporter is embedded. Subtle aspects of their preparation can shift their limit of detection by orders of magnitude. In this protocol, we present the optimized, step-by-step procedure for generating reproducible SERRS nanoparticles with femtomolar (10-15 M) limits of detection. We provide ways of characterizing the optical properties of SERRS nanoparticles using UV/VIS and Raman spectroscopy, and their physicochemical properties using transmission electron microscopy and nanoparticle tracking analysis. We introduce several applications of these nanoprobes for biomedical research, with a focus on intraoperative cancer imaging via Raman imaging. A detailed account is provided for successful i.v. administration of SERRS nanoparticles such that delineation of cancerous lesions can be achieved in vivo and ex vivo on resected tissues without the need for specific biomarker targeting. This straightforward, yet comprehensive, protocol-from initial de novo gold nanoparticle synthesis to SERRS nanoparticle contrast-enhanced preclinical Raman imaging in animal models-takes ∼96 h.