Controlling the Energy Relaxation: Organic Doping in AIEgen Nanoparticles for Highly Enhanced Intravital Two‐Photon Imaging

Abstract Aggregation‐induced emission luminogens (AIEgens) as a new class of optical probes for two‐photon imaging (2PI) have attracted extensive attention in the research community. However, their non‐radiative energy dissipation plays a non‐negligible role in energy consumption, thereby weakening their performance in 2PI. Exploration of a facile and general approach to control the energy relaxation pathways is thus a fascinating yet significantly challenging task. To address this concern, an organic doping method is proposed herein by using TPE‐Br as the doping AIEgen and MeOTTMN as the functional AIEgen. With increased amount of doping molecules, a steadily strengthened brightness (up to 29‐fold of quantum yield) is observed at the expense of reactive oxygen species production. Remarkably, an ultradeep imaging depth of 1000 µm in a mouse brain is realized via 2PI using the heavily organic‐doped AIEgen(ODA) nanoparticles (NPs). Such result is far superior to the imaging depth of 156 µm enabled by MeOTTMN NPs. The safe use of ODA NPs is further evaluated by in vitro and in vivo toxicity assessment. This study thus provides an attractive paradigm to control the energy relaxation of AIEgen NPs and maximize their performance in 2PI while circumventing the difficulties in molecular engineering.