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

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.