Highly Sensitive Near-Infrared SERS Nanoprobes for in Vivo Imaging Using Gold-Assembled Silica Nanoparticles with Controllable Nanogaps

Abstract Backgroud: Surface-enhanced Raman scattering (SERS) imaging is widely exploited, given its advantages such as multiplex capacity, non-photobleaching property, and high sensitivity. Near-infrared (NIR) radiation is suitable for in vivo studies because it exhibits good tissue penetration capability. Results In this study, gold (Au)-assembled silica (SiO2) nanoparticles (SiO2@Au@Au NPs) as NIR SERS nanoprobes are synthesized by a seed-mediated growth method. SiO2@Au@Au NPs with six different sizes of Au NPs are prepared by controlling the concentration of the Au precursor in the growth step. Therefore, the surface plasmonic band of the nanogaps between Au NPs on the SiO2 surface could be controlled from 4.16 to 0.98 nm, thus generating SERS hotspots. SiO2@Au@Au NPs with a 0.98-nm gap shows high SERS signals after being subjected to an excitation wavelength of 785 nm (enhancement factor ~3.8 × 106). SiO2@Au@Au nanoprobes shows detectable in vivo SERS signals at a concentration of 16 µg/mL in a 7-mm-thick animal tissue specimen. SiO2@Au@Au NPs with 14 different Raman label compounds shows distinguishable SERS signals upon being subcutaneously injected into nude mice. Conclusion Through this study, it is highlighted that their potential for use in in vivo applications as multiplex nanoprobes.