Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging

Abstract

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional images of tissues with high resolution. Although NIR-PAI is promising, its wide application is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represent an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and allows direct functionalization with targeting moieties. The ICG-JA platform has high photostability and a PA-signal amplitude that is two times stronger than whole blood. The targeting ability of ICG-JA was validated in vitro using HeLa cells. The ICG-JA was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 minutes post-injection with a contrast-to-noise ratio of 2.42.