NIR-II Ratiometric\nOptical Theranostic Capsule for <i>In Situ</i> Diagnosis\nand Precise Therapy of Intestinal Inflammation

Capsules were widely used in clinical settings for the\noral delivery\nof various drugs, although it remains challenging to trace real-time\ndrug release behavior and adjust dosages based on the therapeutic\neffect. To address these issues, we developed theranostic capsules\nthat loaded two kinds of fluorescence nanoparticles, H<sub>2</sub>O<sub>2</sub>-responsive Janus Ag/Ag<sub>2</sub>S nanoparticles (Ag/Ag<sub>2</sub>S JNPs) and the downconversion nanoparticles (DCNPs), and\nthe dexamethasone (Dex) drug. The Ag/Ag<sub>2</sub>S JNPs exhibit\na highly sensitive fluorescence (FL) signal at 1250 nm in response\nto H<sub>2</sub>O<sub>2</sub>, while the FL signal from the DCNPs\nat 1550 nm remains stable under physiological conditions. The ratio\nof these two FL signals formed the ratiometric FL signal, which shows\ncorrelation with the H<sub>2</sub>O<sub>2</sub> concentration with\na detection limit of 1.7 μM. Moreover, the capsules can be precisely\ndelivered into the intestine, where they release the JNPs and DCNPs\nsimultaneously. The H<sub>2</sub>O<sub>2</sub>-triggered ratiometric\nFL signals and images can diagnose inflammation and indicate its location.\nMeanwhile, the encapsulated Dex is released in the disease region,\nwith ratiometric imaging allowing for real-time tracking of therapeutic\nefficacy and providing guidance for ongoing treatment. The theranostic\ncapsule system provides an approach for quantitative detection of\ndisease biomarkers and further localized release of therapeutics,\nthereby avoiding overdose and reducing side effects.