Rapid in situ microwave-assisted fabrication of ultrabright near-infrared probe for low-dose in vivo inflammatory imaging

Fluorescent probes operating within the near-infrared second window (NIR-II, 1000–1700 nm), characterized by high tissue transparency and minimal tissue-induced photon scattering/absorption, have been widely applied for early-stage disease diagnosis. However, the capability of NIR-II emitters for deep-tissue imaging is limited by relatively low brightness, which hinders the acquisition of images at low excitation intensity and administration dose. Herein, we introduce a novel in situ strategy to fabricate ultrabright Ag₂S nanoparticles (Ag₂S super NPs) via aftertreatment of chemically synthesized Ag₂S NPs, where a protective shell grown by a 2-minutes rapid microwave irradiation. This shell effectively reduces the surface and structural defects, resulting in a 25-fold promotion of the quantum yield and 38-times increment of the fluorescence lifetime. The nontoxic PEGylated Ag₂S super NPs enable in vivo deep-tissue imaging under low excitation laser (1 mW/cm²) and administration dose (0.5 mg/kg). Furthermore, after the modification with targeting peptide, Ag₂S super NPs exhibit outstanding imaging performance by achieving an over 90% intensity promotion compared to commercial Ag₂S NPs for targeted inflammation imaging in gastritis and myocarditis models. These results present an effective, cost-effective and rapid enhancement approach to obtain ultrabright NIR-II imaging contrast agent, thereby advancing their potential for pre-clinical diagnosis imaging applications.