Bio-compatible contrast agents based on clinically-approved indocyanine green (ICG) can greatly enhance the deep-tissue imaging performance of optoacoustic (OA) imaging systems and facilitate the clinical translation of this modality. In this work, we propose an inverse emulsion approach to synthetize bio-based, bio-degradable nano- and micro-capsules consisting of an aqueous core of ICG and a cross-linked casein shell. The feasibility to visualize and track individual capsules with a diameter of 4-5 micrometers is demonstrated in vitro and in vivo. This can pave the way towards clinical approval of contrast agents capable of being detected at a single-particle level.
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