Tuning long-term mitochondrial imaging and photodynamic therapy capabilities through rational design of aggregation-induced emission luminogens

Many aggregation-induced emission luminogens (AIEgens) not only act as photosensitizers to generate cytotoxic reactive oxygen species under the irradiation of appropriate light, but also emit bright fluorescence for positioning and tracking, realizing image-guided photodynamic therapy. However, few AIEgens can achieve long-term near-infrared bioimaging, and the design of AIEgens rarely involves multi-faceted functional optimization and the combined use of different AIE groups. In this study, a series of low-toxic salicylaldehyde-based Schiff base AIEgens (NPy-AIE, NNPy-AIE, TPy-AIE and TTPy-AIE) are rational designed from multiple aspects to study structure-function relationships, which all exhibit excellent long-term bioimaging capability. Starting from NPy-AIE, its water solubility is enhanced by increasing the number of cations and constructing hydrophilic groups to obtain NNPy-AIE. Dimethylaniline groups of NPy-AIE are replaced with triphenylamine groups to acquire TPy-AIE with enhanced AIE activity. Thiophene groups are introduced in TPy-AIE to obtain TTPy-AIE with larger conjugation structure and electron donor-acceptor strength. The first two red-emitting AIEgens have better long-term mitochondrial targeting capability. NNPy-AIE has better water solubility and mitochondrial membrane potential detection capabilities. In particular, the latter two near-infrared emitting AIEgens can not only achieve long-term in vivo and in vitro near-infrared imaging, but also generate singlet oxygen under white light irradiation, which increases the level of intracellular reactive oxygen species and the proportion of apoptotic cells, showing potential as photosensitizers for image-guided photodynamic therapy. In vivo photodynamic therapy experiment of TTPy-AIE in 4T1 tumor-bearing mice has confirmed its excellent biocompatibility and photodynamic therapy ability.