“Matthew Effect”: General Design Strategy of Fluorogenic Bioorthogonal
Nanoprobes with Ultrahigh Emission Enhancement
Abstract
Fluorescence imaging, a key technique in life science research,
frequently utilizes fluorogenic probes for precise imaging in living
systems. Tetrazine is an effective emission quencher in the design of
fluorogenic probes, which can be selectively damaged upon bioorthogonal
click reactions, leading to considerable emission enhancement. Despite
significant efforts to increase the emission enhancement ratio upon
click reaction (IAC/IBC)
of tetrazine-functionalized fluorogenic probes, the influence of
molecular aggregation on the emission properties has been largely
overlooked in the design of these probes. In this study, we reveal that
an ultrahigh IAC/IBC can
be realized in the aggregate system when tetrazine is paired with
aggregation-induced emission (AIE) luminogens. Tetrazine can increase
its quenching efficiency upon aggregation and drastically reduce
background emissions. Subsequent click reactions damage tetrazine and
trigger significant AIE, leading to considerably enhanced
IAC/IBC. We further
showcase the capability of these ultra-fluorogenic systems in selective
imaging of multiple organelles in living cells. We propose the term
“Matthew Effect” in Aggregate Emission to describe the unique
fluorogenicity of these probes, potentially providing a universal
approach to attain ultrahigh emission enhancements in diverse
fluorogenic aggregate systems.