Miniature Gold Nanorods for Photoacoustic Molecular Imaging in the Second Near-Infrared Optical Window

In photoacoustic imaging, the second near infrared (NIR II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, we synthesize miniaturized gold nanorods absorbing in NIR II that are 5–11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are about three times more thermally stable and generate 3.5 times stronger photoacoustic signal than absorption-matched large counterparts. These unexpected findings are confirmed using theoretical and numerical analysis, showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle solution but also to the surface-to-volume ratio of the nanoparticles. In living tumor bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumors and generate 4.5 times greater photoacoustic contrast.