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

Multimodal contrast agents with high biocompatibility 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, PAI, 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 vivo studies confirm the utility of the [GdO]⁺[ICG]⁻ IOH-NPs for optical and magnetic resonance imaging with a T₁ 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.