Nonlinear photoacoustic signal increase from endocytosis of gold nanoparticles.

Nonlinear photoacoustic effects, rarely seen in biomedical photoacoustic imaging of tissues, can manifest themselves strongly when plasmonic nanoparticles are used as imaging contrast agents. Specifically, nonlinear behavior of photoacoustic signal with modest laser fluences can occur when nanoparticles undergo cellular endocytosis and aggregation leading to thermal coupling and subsequent localized temperature enhancement. Our study demonstrated this effect using in vitro tissue models containing cells. While the photoacoustic signal amplitude was linearly proportional to the cell/nanoparticle concentration, the photoacoustic signal increased nonlinearly as the laser fluence increased. Our results, therefore, suggest that the nonlinear effects can be exploited in molecular/cellular photoacoustic imaging.