A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Xiaoqing Zhou; Lanlan Dong; Baohua Zhao; Guangyun Hu; Can Huang; Tengfei Liu; Yifei Lu; Mengxue Zheng; Yanlan Yu; Zengjun Yang; Shaowen Cheng; Yan Xiong; Gaoxing Luo; Wei Qian; Rui Yin

doi:10.1093/burnst/tkad041

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A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

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- A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms
- A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms
- Burns & Trauma 2023年11卷第1期
- 作者机构：
  
  1. Army Medical University (Third Military Medical University)
  2. Southwest Hospital, Army Medical University (Third Military Medical University)
  3. No. Hospital of Joint Logistic Support Force of PLA,906
  4. the First Affiliated Hospital of Hainan Medical University
- 作者简介：
- 基金信息：
  
  This work was supported by the National Natural Science Foundation of China (Grant No. 82172203), the Natural Science Foundation of Chongqing (Grant No. cstc2020jcyj-msxmX0435, cstc2019jcyj-cxttX0001), Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau;Grant No. 2022ZDXM014) and the Talent Programme of Third Military Medical University (Army Medical University;Grant No. XZ-2019-505-065).
- DOI：10.1093/burnst/tkad041
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-10-16，
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Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, 等. A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms[J]. Burns & Trauma, 2023,11(1).

Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, Guangyun Hu, Can Huang, Tengfei Liu, Yifei Lu, Mengxue Zheng, Yanlan Yu, Zengjun Yang, Shaowen Cheng, Yan Xiong, Gaoxing Luo, Wei Qian, Rui Yin, A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms, Burns & Trauma, Volume 11, 2023, tkad041, https://doi.org/10.1093/burnst/tkad041
Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, 等. A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms[J]. Burns & Trauma, 2023,11(1). DOI： 10.1093/burnst/tkad041.

Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, Guangyun Hu, Can Huang, Tengfei Liu, Yifei Lu, Mengxue Zheng, Yanlan Yu, Zengjun Yang, Shaowen Cheng, Yan Xiong, Gaoxing Luo, Wei Qian, Rui Yin, A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms, Burns & Trauma, Volume 11, 2023, tkad041, https://doi.org/10.1093/burnst/tkad041 DOI：

摘要

Abstract

BackgroundMultidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover

the formation of biofilms makes these bacteria difficult to control. Therefore

developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N

N′-di-sec-butyl-N

N′- dinitroso-1

4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.MethodsThe characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay

plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay

Calcein/PI cytotoxicity assay

hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.ResultsHerein

we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT)

photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser

IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation

which further reacted with ROS to generate ONOO−

leading to the enhancement of bactericidal efficacy. Furthermore

NO and ONOO− could disrupt the cell membrane

which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study

IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections

relief of inflammation

promotion of re-epithelization and collagen deposition

and regulation of angiogenesis during wound healing. Moreover

IRNB exhibited excellent biocompatibility

both in vitro and in vivo.ConclusionsThe present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

关键词

Keywords

Photothermal therapyPhotodynamic therapyNitric oxideSynergisticBoronic acidMultidrug-resistant gram-negative bacteria

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