Activity-Based Luciferase-Luciferin Bioluminescence System for Bioimaging Applications

Abstract

There is growing interest in applying bioluminescence for imaging varies biological processes in life sciences due to its high resolution, selectivity, and signal/noise ratio (no need of external light excitation). Among the diverse bioluminescence systems, firefly luciferin–luciferase system is considered to be the most popular one for bioimaging applications both in vitro and in vivo. The general design strategy of this system is to cage luciferin (i. e., free luciferin is protected with distinctive functional groups). When the protecting moieties are removed by their corresponding analytes, bioluminescence signal turns “on”, enabling people to understand their biological processes. Considering that d-luciferin-luciferase bioluminescence imaging system is now becoming a hot and cutting-edge research topic, in this minireview, we briefly explain the bioluminescence mechanism and summarize the biological molecule-responsive, d-luciferin-based bioluminescence imaging probes. Moreover, the attempts to optimize the photochemical properties of d -luciferin are also introduced. Current challenges and future perspectives for activity-based luciferase-luciferin bioluminescence system are also outlooked. With the understanding of the structure−property relationships and working mechanisms of these bioluminescence probes, we hope that this minireview might provide effective guidance for the development of bioluminescence imaging probes and even their clinical translations.