Portfolio of colloidally stable gold-gold sulfide nanoparticles and their use in broad-band photoacoustic imaging

There is an increasing interest in non-invasive photoacoustic imaging and hence demand for non-toxic, stable, optical solid absorbers, particularly in the visible and near-infrared regions enabling deep tissue penetration. The most popular gold nanorods (GNR) suffer from cumbersome synthesis with poor reproducibility and stability under moderate laser exposure. Recently, a new class of nanoparticle, gold-gold sulfide (GGS), was recognized to have strong NIR absorption but lack colloidal stability. Here, we successfully synthesized a portfolio of aqueous GGS nanoparticles (NP) with excellent stability through a one-step, reproducible synthesis: Anionic, cationic, and protein-coated GGS NPs were obtained by using 3-mercaptopropionic acid (3MPA), branched poly(ethyleneimine) (bPEI) and bovine serum albumin (BSA) as a coating. All GGS NPs comprise small (30 nm) morphologies and display two absorption bands centered at 530-540 nm and 800-900 nm. The photoacoustic activity (PA) of GGS NPs in solution at the visible (532 nm) and NIR (800 nm) region is similar and independent of the coating. Remarkably, they outperformed the spherical gold NPs and performed comparable to GNRs. PA microscopy images recorded with visible and NIR lasers revealed that GGS NPs are successfully internalized by triple-negative MDA-MB-231 breast cancer cells, used for the proof of principle. A coating-dependent intracellular PA signal in favor of GGS-3MPA was observed. The weakest signal was obtained with the GGS-BSA, indicating a low cellular uptake. These stable, aqueous GGS NPs emerge as promising candidates for broad-band PAI and further biomedical applications.