High-Performance Near-Infrared Aggregation-Induced Emission Luminogen with Mitophagy Regulating Capability for Multimodal Cancer Theranostics

The construction of intelligent near-infrared
(NIR) fluorophores
for high specificity to cancer cells and application in multiple therapeutic
modalities is crucial for precise cancer diagnostic and therapy. In
this study, an aggregation-induced emission-active NIR fluorophore
(TACQ) with mitophagy-modulating activity was synthesized and developed
for mitochondrial targeting multimodal cancer theranostics. The strengthened
push–pull interaction extended the emission of TACQ into the
NIR-II region (>1000 nm). Further, the rotor structure and twisted
molecular conformation enables nanoaggregates of TACQ to balance the
radiative and nonradiative decays to simultaneously exhibit bright
NIR emission, high photothermal conversion efficiency (55%), and efficient
generation of reactive oxygen species. The lipocationic property of
TACQ allows it to selectively accumulate in the mitochondria of cancer
cells. TACQ can induce mitophagy and block mitophagic flux facilitating
cancer cell apoptosis. Both in vitro and in vivo evaluations revealed that TACQ is an efficient theranostic
agent for NIR fluorescence and photothermal imaging-guided synergistic
chemo-photothermal and photodynamic therapy.