Abstract

We introduce a dual imaging contrast agent for ultrasound and photoacoustic (US/PA) imaging. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were previously applied to photoacoustic imaging of lymph node mapping and cancer cell visualization. Based on the enhanced cellular uptake, strong photoacoustic signal was observed. Using this nanoparticle platform, we developed a gas-generating nanoconstruct consisting of GC-AuNP and azide compounds that produce gas upon laser irradiation. The gas-generating nanoparticles have unique properties desired for ultrasound imaging. Compared with conventional ultrasound contrast agents (i.e., microbubbles), the novel contrast agent is superior in terms of nanometer-scale size and controlled gas generation. We showed that the developed nanoparticles were feasible as an ultrasound imaging contrast agent with signal enhancement caused by laser-triggered nitrogen gas generation. More importantly, the signal enhancement was controlled through the intensity and duration of excitation laser pulses. Overall, the discovery of the photocatalytic function of gold nanoparticles in the photolysis of azide enabled synthesis of the gas-generating contrast agent consisting of less than 50 nm diameter particles. Our results strongly suggested that gas-generating nanoparticles will allow ultrasound imaging of various diseases that conventional ultrasound contrast agents cannot reach and, therefore, detect, diagnose, and characterize. In addition, the plasmonic core of the developed nanoparticles serves as contrast agent for photoacoustic imaging and allow for further increase of diagnostic sensitivity of combined US/PA imaging. Broadly, the developed gas-generating nanoparticles may play critical role in various applications of light and sound ranging from diagnostic imaging to image-guided therapy.

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