Photostable, hydrophilic, and near infrared quaterrylene-based dyes for photoacoustic imaging

Highlights: • Two types of quaterrylene-based NIR dye were developed as photoacoustic agents. • Both dendrimeric and small molecule cationic dye exhibit superior photo-stability. • Small molecule cationic dye shows a high cellular uptake binding to mitochondria. - Abstract: Novel near-infrared contrast agents based on the quaterrylene structure were strategically developed and tested for high photo-stability. Both a dendrimeric quaterrylene molecule, QR-G2-COOH, and a small molecule cationic quaterrylene dye, QR-4PyC4, remain optically stable and continue to generate a competitive photoacoustic response when irradiated by short near-infrared laser pulses for a relatively long time in an in-vitro cell study, unlike indocyanine green that rapidly decreases photoacoustic signal amplitude. The small molecule dye, QR-4PyC4 exhibits not only significantly higher cellular uptake rate than QR-G2-COOH and indocyanine green, but also low toxicity at a concentration of up to 10 μM. The dendrimeric dye, QR-G2-COOH that has surface functional groups available for conjugation with targeting and therapeutic agents shows the highest photoacoustic amplitude with high optical stability. Therefore, QR-4PyC4 can be a promising universal, sensitive and reliable photoacoustic contrast agent and QR-G2-COOH has great potential as a nano-platform with stable photoacoustic imaging capability.