Quantitative Surface-Enhanced Resonant Raman Scattering Multiplexing of Biocompatible Gold Nanostars for in Vitro and ex Vivo Detection

Abstract

Surface-enhanced Raman scattering (SERS)-active plasmonic nanomaterials have become a promising agent for molecular imaging and multiplex detection. To produce strong SERS intensity while retaining the non-aggregated state and biocompatibility needed for bioapplications, we integrated near infrared (NIR) responsive plasmonic gold nanostars with resonant dyes for resonant SERS (SERRS). The SERRS on nanostars was several orders of magnitude greater than signals from SERRS on nanospheres and non-resonant SERS on nanostars. For the first time, we demonstrated quantitative multiplex detection using 4 unique nanostar SERRS probes in both in vitro solutions and ex vivo tissue samples under NIR excitation. With further optimization, in vivo tracking of multiple SERRS probes is possible.

Gold Nanosensitisers for Multimodal Optical Diagnostic Imaging and Therapy of Cancer

“…BSA, in its denatured form, was found to be more advantageous in that its thiol binding capacity was found to be much stronger and maintained the non-aggregated isolated state of the nanostructures even after multiple washes. In the study by Yuan et al nanoparticle tracking analyses (NTA) confirmed this and also showed that PEG stabilised nanoconstructs tend to form small clusters after multiple washes [9]. The stabilizing property of BSA stems from the exposed thiol groups.…”

“…Various biopolymers have been reported as stabilisers, but polyethylene glycol (PEG) and bovine serum albumin (BSA) have been recently exploited for their enhanced biocompatibility [9,28]. PEG covering has been shown to stabilise gold nanoparticles and shield the Raman reporter due to the specific adherence on gold nanoparticle's surface that spontaneously forms a monolayer on gold [29].…”

“…These can be attained by chemical denaturation of BSA which converts the multiple disulphide (S-S) bonds to functional thiol groups (-SH). These have been widely reported to have high affinity for the gold nanoparticle surface [9,30]. To prevent fluorescence quenching of photosensitisers (PS) by nanostars [31,32] and to stabilise the nanoconstruct, dBSA was first conjugated with hypericin and the dBSA -hypericin complex was then conjugated with the DTTCI tagged nanostars.…”

“…This acts to significantly enhance the electromagnetic field intensity. This property called localised surface plasmon resonance (LSPR) in turn enhances the scattering crosssection of the nanostars and of the molecules adsorbed, an effect called surface enhanced Raman scattering (SERS) [8][9][10]. Bioimaging based on SERS tags has attracted growing interest recently.…”

Monitoring the penetration and accumulation of gold nanoparticles in rat skin ex vivo using surface-enhanced Raman scattering spectroscopy

“…The enhancements on nanostars or nanoaggregates was several orders of magnitude greater than the SERS signals from nanospheres. 40,41 The nanoaggregates yielded large enhancements due to the generation of the EM \hot spots" between two nanospheres. And the highest SERS enhancements had been obtained on aggregates or clusters formed by individual silver or GNPs 20-60 nm in size.…”