Novel Indocyanine Green Based Nanosensors for Photoacoustic Imaging and Sensing

Photoacoustic imaging (PAI) is an immerging imaging modality that combines the molecular specificity of optical imaging techniques with the penetration depth of ultrasound. Leveraging ultrasound detection, PAI can provide anatomical and functional information of the tissue at centimeters in depth. To help facilitate deep tissue excitation, PAI would benefit from a near-infrared (NIR) absorbing contrast agent (CA). However, there are few NIR absorbing CAs for biological imaging with the necessary properties for PAI. Indocyanine Green (ICG) is an FDA approved NIR absorbing dye used in many clinical and preclinical applications. However, ICG exhibits photobleaching, non-specific binding, short circulation times (limited imaging time) and concentration dependent optical properties. This research sought to mitigate the concentration dependent optical properties of ICG for PAI. We examined novel strategies for synthesizing ICG-based nanoparticles that rely on direct aggregation of dye or templating of dye molecules on DNA-based nanostructure. J-aggregates (JA) are formed by the highly ordered assembly of organic dyes (such as ICG). ICG JA are known for their sharp NIR absorption peak at 895 nm and improved optical stability over ICG. We developed a facile synthesis method for azide-modified ICG JA. This synthesis delivered size turnability (1.2 um to 230 nm) and direct functionalization with targeting moieties. Using an RGD modified version, we were able to procure 3D PAI images in vivo with a contrast-to-noise ratio of 2.42 in blood vessels as deep as 5 mm from the surface of the skin of a nude mouse. Using DNA origami, we were able to precisely control the density of ICG monomers on a DNA scaffold. This fixed the NIR absorption of ICG monomers and allowed for functionalization of targeting moieties. The optical properties, stability in blood, and voltage sensing capabilities were characterized. This research then compared the optical properties of a few novel ICG-based CAs against free ICG in saline and blood. Further in vitro and in vivo validation and development continues for progression into preclinical and clinical arenas.

Author

• Giammanco, Giovanni Scott

• DNA origami
• Indocyanine Green
• J-aggregate
• Nanosensor
• Photoacoustic imaging
• Voltage sensor

Identifier

hdl:1920/14780

OAI identifier oai:identifier

oai:MARS:1920/14780