Structure-oriented design strategy to construct NIR AIEgens to selectively combat gram (+) multidrug-resistant...

Area of Science:

• Biomedical Engineering
• Materials Science
• Infectious Diseases

Background:

• Multidrug-resistant (MDR) gram-positive bacteria pose a significant threat in healthcare settings, necessitating novel therapeutic strategies.
• Current treatments, including antibiotics, face challenges due to rising resistance.
• Developing targeted agents for effective in vivo infection control is crucial.

Purpose of the Study:

• To design and synthesize a novel organic photo-antimicrobial near-infrared (NIR) AIEgen (aggregation-induced emission gen) named BDPTV.
• To investigate BDPTV's ability to specifically target and eliminate MDR gram-positive bacteria through a structure-oriented design strategy (SODS).
• To evaluate BDPTV's efficacy in combating bacterial infections in vitro and in vivo.

Main Methods:

• A structure-oriented design strategy (SODS) was employed to construct BDPTV, incorporating a phenylboronic acid moiety for bacterial cell wall binding.
• The photo-antimicrobial activity of BDPTV was assessed by measuring reactive oxygen species (ROS) generation upon photoirradiation.
• In vitro studies utilized methicillin-resistant Staphylococcus aureus (MRSA), while in vivo studies involved MRSA- and Escherichia coli (E. coli)-infected mouse wound models.

Main Results:

• BDPTV demonstrated specific binding to the peptidoglycan layer of MDR gram-positive bacteria, leading to localized accumulation.
• Photoirradiation of BDPTV generated abundant ROS, effectively destroying MRSA through photodynamic therapy, outperforming commercial photosensitizers and antibiotics.
• In vivo experiments showed BDPTV successfully treated MRSA-infected wounds in mice, with no significant effect on E. coli-infected wounds.

Conclusions:

• The developed AIEgen, BDPTV, shows high efficacy against MDR gram-positive bacteria via photodynamic therapy.
• The SODS approach provides a viable strategy for designing targeted antimicrobial agents.
• This research offers a potential new method to combat antibiotic resistance and reduce antibiotic overuse.