4.7 Article

Cancer imaging using surface-enhanced resonance Raman scattering nanoparticles

Journal

NATURE PROTOCOLS
Volume 12, Issue 7, Pages 1400-1414

Publisher

NATURE PORTFOLIO
DOI: 10.1038/nprot.2017.031

Keywords

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Funding

  1. NIH [R01 EB017748, K08 CA16396]
  2. Dana Foundation Brain and Immuno-Imaging Grant
  3. Dana Neuroscience Scholar Award
  4. MSKCC Brain Tumor Center Grant
  5. MSKCC Center for Molecular Imaging and Nanotechnology Grant
  6. MSKCC Technology Development Grant
  7. Commonwealth Foundation for Cancer Research
  8. Center for Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center
  9. Geoffrey Beene Cancer Research Center at MSKCC Grant
  10. Shared Resources Award
  11. RSNA Research Scholar Grant
  12. Society of MSKCC Research Grant
  13. National Natural Science Foundation [81401461]
  14. MSKCC NIH [P30-CA008748]
  15. Damon Runyon Cancer Research Foundation [DRR-29-14]

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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, protocolfrom initial de novo gold nanoparticle synthesis to SERRS nanoparticle contrast-enhanced preclinical Raman imaging in animal modelstakes similar to 96 h.

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