Dimeric Gold Nanoparticle Assemblies as Tags for SERS-Based Cancer Detection

Herein, a new class of multifunctional materials combining a clustered nanoparticle‐based probe is presented for surface enhanced Raman scattering (SERS)‐based microscopy and surface functionalization for tissue targeting. Controlled assembly of spherical gold nanoparticles into dimers (DNP‐REP) is engineered using a small, rigid Raman‐active dithiolated linking reporter (REP) to yield narrow internanoparticle gaps and to strategically generate the “hot spot” while concurrently placing the reporter within the region of highest SERS enhancement. Peptide functionalized DNP‐REP materials are highly stable even upon incubation with living cells and show controlled levels of binding and intracellular endocytosis. To demonstrate the functionality of such probes for disease detection, differentially targeted DNP‐REPs are incubated over various time points with cultured human glioblastoma cells. Using human glioblastoma cells, the SERS maps of targeted tumor cells show the markedly enhanced signals of the DNP‐REP, compared to conventional confocal fluorescence based approaches, especially at low incubation times. Even with as few as 40 internalized DNP‐REP, a relatively intense SERS signal is measured, demonstrating the high signal to noise ratio and inherent biocompatibility of the materials. Thus, these Raman reporter‐based nanoparticle cluster probes present a promising and versatile optical imaging tool for fast, reliable, selective, and ultrasensitive tissue targeting and disease detection and screening. Dimers of gold nanoparticles are employed to build surface enhanced Raman scattering (SERS)‐based tags. The nanoparticles are held together by a small Raman‐active molecular linker and surface‐functionalized with stabilizing polyethylene glycol, fluorescent dyes, and cell‐specific targeting moieties. Upon incubation with cancerous cells, the tags demonstrate high sensitivity at low incubation times, high selectivity, retained activity upon endocytosis, low cytotoxicity, and more effective tumor phenotype detection compared to traditional fluorescence‐ based approaches.