Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders

Precise and noninvasive theranostic methods to quantify and deplete focal iron are of crucial importance for iron-overload disorders. Here, we developed an indocyanine green (ICG)–based imaging platform to reveal Fe³⁺ in vitro and in vivo. The high sensitivity and specificity of ICG-Fe interaction facilitated MR images with a marked correlation between T₁ signal intensity ratio (T₁SIR) changes and Fe³⁺ concentration in rodent models and humans. On the basis of these findings, a rational design for coordination-driven self-assembly ICG-Lecithin (ICG/Leci) was proposed to determine Fe³⁺. The enhancement of photoacoustic signal at 890 nm with increasing Fe³⁺ concentration showed an over 600% higher linear slope than that of T₁SIR changes in animal models. ICG/Leci also promoted a 100% increase in iron depletion in the liver compared with deferoxamine. The high MR sensitivity and superior photoacoustic contrast, combined with enhanced iron depletion, demonstrate that ICG/Leci is a promising theranostic agent for simultaneous detection and treatment of iron-overload disorders.