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 <i>in vitro</i> and <i>in vivo</i> evaluations revealed that TACQ is an efficient theranostic agent for NIR fluorescence and photothermal imaging-guided synergistic chemo-photothermal and photodynamic therapy.