Microenvironment‐Tailored Catalytic Nanoprobe for Ratiometric NIR‐II Fluorescence/Photoacoustic Imaging of H 2 O 2 in Tumor and Lymphatic Metastasis

Abstract In vivo H 2 O 2 visualization is crucial for disease diagnosis. Catalytic reaction‐based probes show potential in H 2 O 2 detection, yet their in vivo application remains challenging because catalysts always require a specific pH to function and cellular glutathione (GSH) may suppress signaling by depletion of hydroxyl radicals and oxidized substrates. Here, a microenvironment‐tailored catalytic nanoprobe (MTCN) comprising Fe 2+ , citric acid (CA), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS), and downconversion nanoparticles in the liposomal cavity as well as a reference dye in the lipid membrane is reported, which utilizes the selective permeability of the liposomal membrane to offer a favorable pH for Fe 2+ catalyst with the aid of CA and to avoid GSH‐triggered signal loss by preventing entry of GSH into the cavity. The MTCN displays a large NIR‐II fluorescence (FL) ratio between 1550 and 1080 nm (FL 1550Em,808Ex /FL 1080Em,980Ex ), but a small photoacoustic (PA) ratio between 808 and 1048 nm (PA 808 /PA 1048 ). Upon exposure of MTCN to H 2 O 2 , catalytic conversion of ABTS into its oxidized form ABTS· + with 808 nm absorption causes a noticeable increment in PA 808 /PA 1048 accompanied by an apparent decrement in FL 1550Em,808Ex /FL 1080Em,980Ex , enabling bimodal ratiometric imaging of H 2 O 2 in the tumor and lymphatic metastasis.