Drug-induced hepatic damage has drawn great attention on public health problems. Drugs are biotransformed in liver by enzymatic processes, accompanied by the production of reactive free radicals, which is the main cause of drug-induced hepatotoxicity. However, the limited penetration of optics make the use of current luminescent imaging more difficult for acquiring free radicals mapping for lesion location, when applied to whole-body imaging in vivo. In this work, we develop an activatable nanoprobe based on Prussian Blue (PB) that can combine magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for deep-tissue ONOO- imaging. We discover that ONOO- can oxidize FeII within PB into FeIII and meanwhile destroy the crystal structure of PB, so that the strong absorption of PB at 710 nm originated from the electron transferring between FeII and FeIII is greatly diminished. As a result, the reduced photoacoustic imaging (PA) signal of PB is able to function as an indicator for sensing ONOO-. Importantly, after reaction with ONOO-, the reduced size of PB result in the decrease of rotational correlation time (τR), leading to the activatable MRI signal for sensing ONOO-. Finally, we demonstrated PB nanoprobe is successfully able to image the variation of ONOO- in drug-induced hepatotoxicity in vivo by PAI and MRI bimodal imaging. Notably, the complementarity of such dual-modality imaging could not only endow our probes with better accuracy and higher penetration depth for visualizing of ONOO- in drug-induced liver injury, but also provide anatomical structure to identify the injury area of livers.

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