Gold Nanostars with Reduced Fouling Facilitate Small Molecule Detection in the Presence of Protein

Gold nanoparticles have the potential to be used in biomedical applications from diagnostics to drug delivery. However, interactions of gold nanoparticles with different biomolecules in the cellular environment result in the formation of a “protein corona”—a layer of protein formed around a nanoparticle, which induces changes in the properties of nanoparticles. In this work we developed methods to reproducibly synthesize spheroidal and star-shaped gold nanoparticles, and carried out a physico-chemical characterization of synthesized anionic gold nanospheroids and gold nanostars through transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential (ZP), nanoparticles tracking analysis (NTA), ultraviolet-visible (UV–Vis) spectroscopy and estimates of surface-enhanced Raman spectroscopy (SERS) signal enhancement ability. We analyzed how they interact with proteins after pre-incubation with bovine serum albumin (BSA) via UV–Vis, DLS, ZP, NTA, SERS, cryogenic TEM (cryo-TEM) and circular dichroism (CD) spectroscopy. The tests demonstrated that the protein adsorption on the particles’ surfaces was different for spheroidal and star shaped particles. In our experiments, star shaped particles limited the protein corona formation at SERS “hot spots”. This benefits the small-molecule sensing of nanostars in biological media. This work adds more understanding about protein corona formation on gold nanoparticles of different shapes in biological media, and therefore guides design of particles for studies in vitro and in vivo.