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In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags

Abstract

We describe biocompatible and nontoxic nanoparticles for in vivo tumor targeting and detection based on pegylated gold nanoparticles and surface-enhanced Raman scattering (SERS). Colloidal gold has been safely used to treat rheumatoid arthritis for 50 years, and has recently been found to amplify the efficiency of Raman scattering by 14–15 orders of magnitude. Here we show that large optical enhancements can be achieved under in vivo conditions for tumor detection in live animals. An important finding is that small-molecule Raman reporters such as organic dyes were not displaced but were stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles were considerably brighter than semiconductor quantum dots with light emission in the near-infrared window. When conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies, the conjugated nanoparticles were able to target tumor biomarkers such as epidermal growth factor receptors on human cancer cells and in xenograft tumor models.

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Figure 1: Design, preparation and properties of pegylated gold nanoparticles for in vivo tumor targeting and spectroscopic detection.
Figure 2: Comparison of pegylated SERS nanoparticles and near-infrared-emitting quantum dots in the spectral region of 650–750 nm.
Figure 3: Cancer cell targeting and spectroscopic detection by using antibody-conjugated SERS nanoparticles.
Figure 4: In vivo SERS spectra obtained from pegylated gold nanoparticles injected into subcutaneous and deep muscular sites in live animals.
Figure 5: In vivo cancer targeting and surface-enhanced Raman detection by using ScFv-antibody conjugated gold nanoparticles that recognize the tumor biomarker EGFR.
Figure 6: Biodistribution data of targeted and nontargeted gold nanoparticles in major organs at 5 h after injection as measured by inductively coupled plasma-mass spectrometry (ICP-MS).

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Acknowledgements

We are grateful to Gregory Adams at Fox Chase Cancer Center for providing the ScFv B10 plasmid construct, to H.Z. Zhang for tumor cell injection, and to Hong Yi for assistance with TEM. This work was supported by grants from the US Air Force Office Multi-University Research Initiative, the National Cancer Institute Centers of Cancer Nanotechnology Excellence (CCNE) Program (U54CA119338 to S.N.), and the National Cancer Institute SPORE Program in Head and Neck Cancer (P50CA128613 to D.M.S.). Four of us (M.D.W., G.Z.C., D.M.S. and S.N.) also acknowledge the Georgia Cancer Coalition (GCC) for distinguished cancer scholar awards. The human carcinoma cells line Tu686 was kindly provided by Peter G. Sacks (New York University College of Dentistry, New York, NY).

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Correspondence to Shuming Nie.

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Qian, X., Peng, XH., Ansari, D. et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol 26, 83–90 (2008). https://doi.org/10.1038/nbt1377

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