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

Authors
 Haidong Li  ;  Mengyao Yang  ;  Ji Seon Kim  ;  Jeongsun Ha  ;  Jingjing Han  ;  Heejeong Kim  ;  Yejin Cho  ;  Jingyun Wang  ;  Ki Taek Nam  ;  Juyoung Yoon 
Citation
 BIOMATERIALS, Vol.286 : 121580, 2022-07 
Journal Title
BIOMATERIALS
ISSN
 0142-9612 
Issue Date
2022-07
MeSH
Animals ; Anti-Bacterial Agents / pharmacology ; Anti-Bacterial Agents / therapeutic use ; Drug Resistance, Multiple, Bacterial ; Escherichia coli ; Humans ; Methicillin-Resistant Staphylococcus aureus* ; Mice ; Photosensitizing Agents / pharmacology
Keywords
Aggregation-induced emission ; In vivo ; Multidrug-resistant bacteria ; NIR fluorescence.
Abstract
Multidrug-resistant (MDR) gram-positive bacteria are an inevitable source of infection for hospitalized patients and one of the reasons for the increased proportion of severe diseases. Therefore, constructing smart agents for specific and effective combating infections in vivo caused by MDR gram-positive strains is very urgent. Herein, we reported a structure-oriented design strategy (SODS) to reasonably construct an organic photo-antimicrobial near-infrared (NIR) AIEgen BDPTV equipped with a phenylboronic acid moiety, which could be bound to the thick peptidoglycan layer of MDR gram-positive bacteria, resulting in a tight distribution with the cell wall in a confined space. Compared to the contrast compounds DQVTA and DPTVN, upon photoirradiation of AIEgen BDPTV, the generation of abundant and highly toxic reactive oxygen species (ROS) irreversibly destroys MDR gram-positive bacteria through photodynamic therapy, which is better than commercial photosensitizers (including methylene blue, chlorin e6, and protoporphyrin IX) and antibiotic (cefoxitin). As a proof of concept, in vitro experimental results showed that methicillin-resistant Staphylococcus aureus (MRSA) were completely killed using AIEgen BDPTV. More importantly, AIEgen BDPTV was capable of successfully combating MRSA-infected wounds of mice, but not Escherichia coli (E. coli)-infected wounds. We hope that this strategy could provide a new method to design powerful AIEgens to avoid the overuse and misuse of antibiotics.
Full Text
https://www.sciencedirect.com/science/article/pii/S0142961222002204?via%3Dihub
DOI
10.1016/j.biomaterials.2022.121580
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188627
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