Biobased Agents for Single‐Particle Detection with Optoacoustics

Abstract

Optoacoustic (OA, photoacoustic) imaging capitalizes on the low scattering of ultrasound within biological tissues to provide high-resolution optical contrast at depths not reachable with optical microscopy. [1][2][3] OA has been widely used to visualize vascular networks, quantify oxygen saturation levels, and characterize healthy and diseased tissues based exclusively on the endogenous contrast provided by hemoglobin, melanin, lipids, and other chromophores. [4][5][6] However, the unique advantages of state-of-the-art OA systems stemming from the multi-spectral (multi-wavelength) and dynamic imaging capabilities can only be fully exploited with extrinsically-administered contrast agents. Contrast-enhanced OA imaging can improve the visibility of blood vessels, organs, and tissues, particularly in deep regions where light is significantly attenuated. [7,8] Optoacoustic (OA, photoacoustic) imaging synergistically combines rich optical contrast with the resolution of ultrasound within light-scattering biological tissues. Contrast agents have become essential to boost deep-tissue OA sensitivity and fully exploit the capabilities of state-of-the-art OA imaging systems, thus facilitating the clinical translation of this modality. Inorganic particles with sizes of several microns can also be individually localized and tracked, thus enabling new applications in drug delivery, microrobotics, or super-resolution imaging. However, significant concerns have been raised regarding the low bio-degradability and potential toxic effects of inorganic particles. Bio-based, biodegradable nano-and microcapsules consisting of an aqueous core with clinically-approved indocyanine green (ICG) and a crosslinked casein shell obtained in an inverse emulsion approach are introduced. The feasibility to provide contrast-enhanced in vivo OA imaging with nanocapsules as well as localizing and tracking individual larger microcapsules of 4-5 µm is demonstrated. All components of the developed capsules are safe for human use and the inverse emulsion approach is known to be compatible with a variety of shell materials and payloads. Hence, the enhanced OA imaging performance can be exploited in multiple biomedical studies and can open a route to clinical approval of agents detectable at a single-particle level.