Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

Abstract

The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer.

Keywords:

• SERS
• gold nanostars
• cancer imaging
• Raman active

Supplementary materials

Figure S1 Transmission electron microscopy image of the nanostars.

Figure S2 Nanostar functionalization characterization using UV–Vis absorption spectroscopy.

Notes: (A) UV–Vis of the nanostars functionalized with a range of different concentrations of DTNB. A second band is appearing due to the formation of TNB⁻. (B) LSPR band of the nanostars functionalized with 0.1 mM DTNB for different salt concentrations, showing the nanostar instability by a decrease in intensity.

Abbreviations: DTNB, 5,5-dithio-bis-(2-nitrobenzoic acid); LSPR, localized surface plasmon resonance; TNB, 3-thio-6-nitrobenzoate; UV–Vis, ultraviolet–visible.

Figure S3 Picture of the nanostars SAM DTNB (A) and nanostars DTNB (B) suspension in 1 M NaCl.

Abbreviations: SAM, self-assembled monolayer; DTNB, 5,5-dithio-bis-(2-nitro-benzoic acid).

Figure S4 Transmission electron microscopy image showing the uptake of the nanostars within vesicular structures of the cell.

Figure S5 (A) picture of the tumor-bearing animals. (B) Magnetic resonance image of animals showing the two tumors, one in each limb. (C) In vivo bioluminescence image illustrated in a color-coded intensity map.

Table S1 For a given set of DTNB concentrations, the LSPR band shift and hydrodynamic diameter increase are reported together with the maximum salt concentration at which the nanostars remain in suspension

Acknowledgments

The authors are grateful for the financial support provided by the Flemish Foundation for Innovation, Science and Technology for the IWT SBO ‘Imagine’ (080017) and IWT SBO ‘NanoCoMIT’ (140061), EM’s PhD scholarship and the University of Leuven for program financing PF IMIR (10/017).

Disclosure

The authors report no conflicts of interest in this work.