Red–Near-Infrared Fluorescent Probe for Time-Resolved in Vivo Alkaline Phosphatase Detection with the Assistance of a Photoresponsive Nanocontainer

Abstract

The monitoring of alkaline phosphatase (ALP) activity in different tissues is significant for disease diagnosis and therapy. However, the time-resolved in vivo sensing of ALP activity remained unresolved. Herein, a novel red-near-infrared fluorescent ALP probe (Cl₂-BDCM-ALP) based on a dichloro-substituted dicyanomethylene-4<i>H</i>-chromene derivative was designed and synthesized with high fluorescence efficiency and stability under biological pH range. By using Cl₂-BDCM-ALP, ALP activity under an acidic microenvironment such as a tumor site can be sensitively imaged, which cannot be achieved by some previously reported ALP probes. By further loading the Cl₂-BDCM-ALP into a near-infrared (NIR) light-responsive nanocontainer, time-resolved long-term imaging of ALP activity was facilely achieved with noninvasive NIR light remote control. Time-resolved variation of ALP activity of the drug-induced acute liver injury mice was successfully monitored in vivo for the first time. This strategy holds great promise in the in situ ALP detection under a broad pH range with temporal resolution.