A Precipitation‐Enhanced Emission (PEE) Strategy for Increasing the Brightness and Reducing the Liver Retention of NIR‐II Fluorophores

Abstract

The lack of organic fluorophores with high quantum yields (QYs) and low liver retention in the second near‐infrared (NIR‐II) window has become a bottleneck in the bioimaging field. An approach to address these problems is proposed by encapsulating phosphorylated fluorescent dyes into biodegradable calcium phosphate nanoparticles. First, an NIR‐II molecule, LJ‐2P, is designed with increased water solubility by introducing two phosphate groups. Meanwhile, LJ‐2P co‐precipitates with calcium ions to form LJ‐2P nanoparticles (NPs). The QYs of LJ‐2P NPs in aqueous solution is increased by 36.57‐fold to 5.12% compared with that of LJ‐2P. This unique phenomenon is named as precipitation‐enhanced emission (PEE), whose detailed mechanism is explored by femtosecond transient absorption. It is demonstrated that co‐precipitation of LJ‐2P with calcium ions changes the micro‐environment, which restricts the molecular rotation and reduces the interaction of water molecules, especially the excited‐state proton transfer. In addition, due to the pH‐sensitive nature, more than 80% of the LJ‐2P NPs are metabolized in the liver within 24 h. Based on the excellent optical properties and good biocompatibility, high‐contrast vascular visualization and breast tumor detecting are achieved. This strategy can apply to other NIR‐II fluorophores to achieve high QYs and low liver retention.

In Vivo Fate of CXCR2-Overexpressing Mesenchymal Stromal/Stem Cells in Pulmonary Diseases Monitored by Near-Infrared Region 2 Imaging

“…2-Bromo-9,9-dimethyl-9 H -fluorene and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi­(1,3,2-dioxaborolane) were purchased from Bidepharm. 4,7-Bis­(7-bromo-2,3-dihydrothieno­[3,4- b ]­[1,4]­dioxin-5-yl)-5,6-dinitrobenzo­[ c ]­[1,2,5]­thiadiazole was synthesized according to our previous work . PLA (202H) was obtained from Daigang.…”

“…In our previous research, we reported a new type of NIR-II fluorescent dye with high quantum yield (QY) and low liver retention based on the precipitation-enhanced emission (PEE) effect. 43 In this study, another high brightness and stability NIR-II molecule, LJ-858, was synthesized and coprecipitated with a poly(D,L-lactic acid) (PLA) polymer to form LJ-858 nanoparticles (NPs). The CXCR2-modified MSCs were efficiently labeled with LJ-858 NPs without affecting their cell viability.…”

“…The application of NIR-II-based photoacoustic imaging to track the targeted migration of MSCs in the inflamed ear model and NIR-II-based FL/PA dual-modal imaging to realize long-term tracking of hUMSCs in an acute liver failure (ALF) model has also been studied. , However, no real-time tracking of genetically engineered MSCs using NIR-II fluorescence dyes in lung diseases has been reported to the best of our knowledge. In our previous research, we reported a new type of NIR-II fluorescent dye with high quantum yield (QY) and low liver retention based on the precipitation-enhanced emission (PEE) effect . In this study, another high brightness and stability NIR-II molecule, LJ-858, was synthesized and coprecipitated with a poly­( d , l -lactic acid) (PLA) polymer to form LJ-858 nanoparticles (NPs).…”