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

Haidong Li, Mengyao Yang, Ji Seon Kim, Jeongsun Ha, Jingjing Han, Heejeong Kim, Yejin Cho, Jingyun Wang, Ki Taek Nam, Juyoung Yoon

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Article number121580
JournalBiomaterials
Volume286
DOIs
StatePublished - Jul 2022

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2021R1A6A1A10039823 and 2022R1A2C3005420 ), the National Research Foundation of Korea (No. 2016M3A9D5A01952416 ), the China Scholarship Council (CSC, No. 201904910820 ), the National Natural Science Foundation of China (No. 22078050 ), and the Fundamental Research Funds for the Central Universities (No. DUT22RC(3)025 ). The animal protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Yonsei University Laboratory Animal Center ( 2020-0233 ). We also thank the Korea Basic Science Institute (KBSI, Ochang, Center of Research Equipment) for supporting the high-resolution mass spectrometry (ESI-HRMS) testing.

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2021R1A6A1A10039823 and 2022R1A2C3005420), the National Research Foundation of Korea (No. 2016M3A9D5A01952416), the China Scholarship Council (CSC, No. 201904910820), the National Natural Science Foundation of China (No. 22078050), and the Fundamental Research Funds for the Central Universities (No. DUT22RC(3)025). The animal protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Yonsei University Laboratory Animal Center (2020-0233). We also thank the Korea Basic Science Institute (KBSI, Ochang, Center of Research Equipment) for supporting the high-resolution mass spectrometry (ESI-HRMS) testing.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

  • Aggregation-induced emission
  • In vivo
  • Multidrug-resistant bacteria
  • NIR fluorescence

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