Molecular photoacoustic imaging with ultra-small gold nanoparticles.

Gold nanoparticles (AuNPs) below 10 nm in size can undergo renal clearance, which could facilitate their clinical translation. However, due to non-linear, direct relationship between their absorption and size, use of such "ultra-small" AuNPs as contrast agents for photoacoustic imaging (PAI) is challenging. This problem is complicated by the tendency of absorption for ultra-small AuNPs to be below the NIR range, which is optimal for in vivo imaging. Herein, we present 5-nm molecularly activated plasmonic nanosensors (MAPS) that produce a strong photoacoustic signal in labeled cancer cells in the NIR, demonstrating the feasibility of sensitive PAI with ultra-small AuNPs.