Tuning the hydrophobicity of pyridinium-based probes to realize the mitochondria-targeted photodynamic therapy and mitophagy tracking

Finely tuning the hydrophobicity of pyridinium-based probes by regulating the length of the alkyl chains on pyridinium unit to achieve the precisely mitochondria-targeted photodynamic therapy and mitophagic tracking through cooperating with electrostatic interaction. [Display omitted] •A series of pyridinium-based probes with high efficiency of ROS generation are rationally designed.•The hydrophobicity of these probes can be finely tuned by modulating the length of the alkyl chains on pyridinium unit.•The precisely mitochondrial targeting can be achieved through adjusting the hydrophobicity of these probes.•The mitochondria-targeted photodynamic therapy and mitophagy tracking can be simultaneously realized by probe TL8C. Targeting mitochondria and dynamically tracking mitophagy are profoundly important in the field of photodynamic therapy (PDT) which relies on the photosensitizers (PSs) under light irradiation. While simultaneously realizing the effective reactive oxygen species (ROS) generation, accurately mitochondrial targeting, and dynamic tracking in a single PS still is a challenging issue. In this context, a series of pyridinium-based cationic fluorogens with aggregation induced emission (AIE) has been developed for this issue. The hydrophobicity of these fluorogens can be finely tuned by modulating the length of the alkyl chains on pyridinium unit. The well-tuned hydrophobicity of TL8C with C8-alkyl chain gives rise to the specifically mitochondrial targeting capability of TL8C based on the appropriate synergistic effect of hydrophobic and electrostatic interaction. Meanwhile, TL8C can produce ROS in high efficiency. The excellent mitochondrial targeting and the effective ROS generation allow TL8C for the specifically mitochondria-targeted PDT as well as the real time monitoring of mitophagy.