Engineered contrast agent platforms for enhanced photoacoustic signal and tumor uptake (Conference Presentation)

Photoacoustic imaging (PAI) can exploit near infrared (NIR) small molecule dyes to enhance contrast for the early identification of cancer with high biocompatibility and minimal toxicity. Unfortunately, the low optical absorption and rapid clearance of small molecule dyes impose considerable limitations for in vivo imaging applications, due to their limited PAI signal generation capabilities in the tumor bed. Using DNA nanotechnology it is possible to precisely position individual dye molecules to tune their intrinsic PAI signal generation capabilities and to engineer nano-carriers that enable targeted delivery and also prolong the lifetime of the contrast agent in vivo. Here, we report the synthesis, characterization and in vivo imaging of DNA nanotechnology-derived nano-carriers that exhibit superior tumor accumulation and photoacoustic (PA) signal generation capabilities when compared to free dyes. The nano-carrier (NC6Q+) comprised of closely positioned IRDye-800CW molecules offers good serum stability and biocompatibility. Absorption and emission measurements show that NC6Q+ exhibits a blue shifted absorption peak at 705nm due to exciton coupling and offers more than 80% fluorescence quenching efficiency. As a result, PAI data from NC6Q+ in tissue mimicking phantoms show a 72% enhancement in PA signal when compared to free IRDye-800CW. In vivo bio-distribution (n=2) and kinetics studies of the nano-carriers indicate 87 % increase in blood retention time compared to free dye, while maintaining renal clearance. Multispectral photoacoustic imaging of tumor bearing mice (n=3) showed 88% enhancement in tumor PA signal for NC6Q+ when compared to free IRDye-800CW. These results suggest that DNA nano-carriers hold promise to create PAI contrast agents with enhanced tumor uptake and PA signal generation capabilities