Gold Nanoraspberries for Surface-Enhanced Raman Scattering: Synthesis, Optimization, and Characterization

In this work, we demonstrate the synthesis of gold nanoraspberries (AuNRB) using a HEPES buffer at room temperature. The study aimed to identify and compare the physicochemical conditions of the AuNRB and gold nanospheres (AuNS) of similar size to a selected set of reporter molecules. The dispersion stability of shape-controlled and AuNS of similar diameters was investigated in three different physiological media, ultrapure water, phosphate-buffered saline (PBS), and fetal bovine serum (FBS), and compared to understand the effect of NP shape, dispersion stability, and surface-enhanced Raman scattering (SERS) enhancement. We have used two nonresonant reporters, trans-1,2-bis(4-pyridyl) ethylene (BPE) and biphenyl-4-thiol (BPT), and a resonant reporter, IR820 (also known as new indocyanine green), a clinically approved dye for diagnostic studies, to explore the relative benefit of using molecular electronic resonance, i.e., comparing SERS vs surface-enhanced resonance Raman scattering (SERRS) with these nanoparticles. SERS has been explored extensively for biomedical applications, but the synthesis of bright gold nanoparticles and the appropriate Raman label is still challenging. To understand and optimize the SERS process, we have characterized both types of gold nanoparticles, ranging from their average size, ζ-potential, and ultraviolet-visible (UV-vis) absorption. It has been found that AuNRB and AuNS are most stable when dispersed in ultrapure water, while significant aggregation of both types has been observed when dispersed in PBS. With 10% FBS, there was a slight shift and increase in the surface plasmon absorbance peak, which resulted from an increase in particle size due to protein corona formation around the gold nanoparticles. For SERS efficiency, it has been found that AuNRB outperform AuNS with all reporters. Further, the resonant reporter, IR820, has provided a higher SERS signal compared to BPE and BPT and with its FDA approval for clinical use is clearly a strong candidate for future in vivo application.