Nonlinear photoacoustic signal increase from endocytosis of gold nanoparticles

Abstract

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.

Fig. 1

(Color online) Diagrams of (a) endocytosis of nanoparticles, (b) disperse nanoparticles before endocytosis, and (c) the local temperature enhancement with thermal coupling around endocytosed nanoparticles.

Fig. 2

(Color online) Normalized absorbance spectra of gold nanoparticles, cells, and endocytosed gold nanoparticles (dashed red, dotted blue, and solid orange lines, respectively). Transmission electron microscopy image of the gold nanoparticles and dark field images of cells with and without nanoparticle loading (dashed red, dotted blue, and solid orange boxes, respectively).

Fig. 3

(Color online) Block diagram of the photoacoustic imaging system and the gelatin tissue-mimicking phantom with gold nanoparticle labeled cell inclusions.

Fig. 4

(Color online) Photoacoustic signal amplitudes from the endocytosed gold nanoparticles in the tissue-mimicking phantom with respect to the cell concentration at wavelengths of (a) 532 nm and (b) 700 nm and with respect to the laser fluence at wavelengths of (c) 532 nm and (d) 700 nm. The dotted lines represent the linear or nonlinear regression fit of the data. The photoacoustic images (5.76 mm × 3.93 mm) from the inclusions with the highest laser fluence in (a) and (b) and with the highest cell concentration in (c) and (d) were incorporated into the graphs.