Multimodal [GdO]+[ICG]- Nanoparticles for Optical, Photoacoustic, and Magnetic Resonance Imaging

Multimodal contrast agents with high bio-compatibility and biodegradability, as well as low material complexity, are in great demand for clinical diagnostics at different scales of resolution and/or for translating preclinical diagnosis into intraoperative imaging. Multimodality, however, often results in multicomponent and multistructured materials with complexity becoming a severe restriction for synthesis, approval, and use in routine clinical practice. Here, we present sulfonate-based saline [GdO](+)[ICG](-) (ICG, indocyanine green) inorganic-organic hybrid nanoparticles (IOH-NPs with an inorganic [GdO](+) cation and an organic [ICG](-) anion) as a novel, multimodality contrast agent for optical, photoacoustic, and magnetic resonance imaging (OI, PAL MRI). [GdO](+)[ICG](-) IOH-NPs have a plain composition based on clinically used constituents and are prepared as an insoluble saline compound in water. The high [ICG](-) content (81 wt %) ensures intense near-infrared emission (780-840 nm) and a strong photoacoustic signal. First, in vitro studies demonstrate longer detectability and greater emission intensity for [GdO](+)[ICG](-) IOH-NP suspensions than for ICG solutions, as well as a reduced toxicity compared to that of Gd-DTPA, a standard MRI contrast agent. Conceptual in viva studies confirm the utility of the [GdO](+)[ICG](-) IOH-NPs for optical and magnetic resonance imaging with a T-1 relaxivity better than that of Gd-DTPA. Taken together, [GdO](+)[ICG](-) represents a new compound and nanomaterial that can be highly interesting as a multimodal contrast agent.