Tuning Optical Properties of BODIPY Dyes by Pyrrole Conjugation for Photoacoustic Imaging

Abstract

Photoacoustic imaging (PAI) is increasingly employed in (pre-) clinical research, thus, development of suitable contrast agents, in particular fluorescence-quenched chromophores, for PAI is of high importance. Small molecule dyes are appropriate due to favorable circulation, excretion properties, and ease of conjugation to targeting moieties. The BODIPY chromophores have been widely used in bioimaging, yet they are not ideal for PAI due to high fluorescence. Hence, here nonfluorescent BODIPY are designed by 1H-pyrrole conjugation (PyBODIPY) to apply as probes for PAI. The PyBODIPYs exhibit absorption maxima up to 800 nm, and PA signal could be detected in concentrations of 1 nmol mL−1 and 35 pmol mm−3, by tube and tissue phantom, respectively. In addition to nonfluorescent, PyBODIPYs are non-phototoxic, photostable, and show high molar extinction coefficients, as well as inertness toward nucleophilic addition. PyBODIPYs are modified with PEG-400, to improve aqueous solubility and to enable in vivo imaging. Thus, PyBODIPY is an attractive small molecule to use as PA contrast agent, which could be coupled to targeting ligands for in vivo use. In addition, 1H-pyrrole conjugation might be applied to the design of novel near-infrared ranged quenchers suitable for PAI, and promote the development of probes for clinical translation.