Molecular Structural Evolution of Near-Infrared Cationic Aggregation- Induced Emission Luminogens: Preclinical Antimicrobial Pathogens Activities and Tissues Regeneration

Increasingly infectious diseases from microbial pathogens (including bacteria and fungi) threaten human health: a situation that has aroused public health concern around the world. Unfortunately, broad-spectrum antimicrobial agents for treatment resistance pathogens and molecular research on their antimicrobial mechanisms are still scarce. Thus, the development of smart agents against microbial infection for surmounting the above dilemmas is an urgent task. In this contribution, we have tactfully designed a family of flexible aggregation-induced emission luminogens (AlEgens) with various alkyl chain lengths and successfully optimized a cationic AlEgen TPA-S-C6NMe(3)(+) based on the molecular relay strategy for killing both bacteria and fungi in vitro with desired results under white light irradiation, superior to traditional commercial photosensitizers including methylene blue, chlorin e6, and protoporphyrin IX. The cationic AlEgen TPA-S-C6-NMe3+ was bound to microbial pathogens via electrostatic and hydrophobic forces and exerted antimicrobial efficacy due to the synergistic effect of alkyl chain length, reactive oxygen species (ROS) generation capability, and two positive charges. Remarkably, AlEgen TPA-S-C6-NMe3+ also exhibited a striking antimicrobial activity in vivo, and promoted the generation of new blood vessels and fibroblasts in bacteria-infected tissues, which was beneficial for wound healing in mice. Overall, we expect that our work could provide a powerful tool against microbial pathogens to avoid infections and to promote tissues regeneration in clinical practice. [GRAPHICS] .

Automated summary

Microbial pathogens pose a threat to human health, and the development of smart agents against microbial infection is urgent. In this study, a family of flexible aggregation-induced emission luminogens was designed, and a cationic AlEgen TPA-S-C6NMe(3)(+) was optimized for killing bacteria and fungi. The AlEgen exerted antimicrobial efficacy through electrostatic and hydrophobic forces, and the synergistic effect of alkyl chain length, reactive oxygen species generation capability, and positive charges. The cationic AlEgen also showed striking antimicrobial activity in vivo and promoted tissue regeneration, benefitting wound healing.