NIR-II AIEgen nanocomplex with suppressed nonradiative decay and intersystem crossing for high-contrast mesenteric vascular imaging

The prompt assessment of the mesenteric vasculature is crucial for the diagnosis of lethal mesenteric ischemia, underscoring the need for real-time mesenteric vascular imaging using small organic molecules that radiate fluorescence within the second near-infrared spectrum (NIR-II) due to its deep penetration and elevated signal-to-background ratio (SBR), which have been rarely reported. Unfortunately, numerous NIR-II dyes exhibit low quantum yields (QYs) when employed in practical applications, highlighting the need for QY enhancement. For this research, a NIR-II fluorescent AIEgen, termed TPETPA-TQT, was rationally designed by incorporating tetraphenylethylene (TPE)-fused triphenylamine (TPA) into the robust, high QY core of 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT). We further encapsulated this dye within F127 to form the TPETPA-TQT F127 nanocomplex, which exhibits a 6.5-fold enhancement in fluorescence intensity over the TPA-TQT dye encapsulated with DSPE-PEG₂₀₀₀, attributed to the suppression of molecular nonradiative decay and intersystem crossing. The abdominal vasculature and microvessels on the intestinal wall surface, as narrow as 0.41 mm, can real-time visualization using TPETPA-TQT F127 nanocomplex, and exhibit a 94 % improvement of SBR versus ICG. Our findings will push forward the progress of high-brightness NIR-II contrast agents for enhanced mesenteric vasculature imaging and mesenteric ischemia diagnosis.