De novo design of highly efficient type-Ⅰ photosensitizer based onπ-conjugated oligomer for photodynamic eradication of multidrug-resistant bacterial infections

Qi Zhao ¹Guangchao Qing ²Jie Yu ³Ying Liu ³Jianliang Shen ⁴Yang Luo ⁵Xingjie Zan ⁴Shengliang Li³

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作者信息

1. State Key Laboratory of Ophthalmology,Optometry and Vision Science,School of Ophthalmology and Optometry,School of Biomedical Engineering,Wenzhou Medical University;Wenzhou Institute,University of Chinese Academy of Sciences;Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou 325001,China;College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China
2. Center of Smart Laboratory and Molecular Medicine,School of Medicine,Chongqing University,Chongqing 400044,China
3. College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China
4. State Key Laboratory of Ophthalmology,Optometry and Vision Science,School of Ophthalmology and Optometry,School of Biomedical Engineering,Wenzhou Medical University;Wenzhou Institute,University of Chinese Academy of Sciences;Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Wenzhou 325001,China
5. Center of Smart Laboratory and Molecular Medicine,School of Medicine,Chongqing University,Chongqing 400044,China;College of Life Science and Laboratory Medicine,Kunming Medical University,Kunming 650050,China
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Abstract

Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible de-sign strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation of 7r-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O2·-)and hydroxyl radical('OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar con-centration under a low white light irradiation(30 mW/cm2).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-Ⅰ photodynamic therapy(PDT)perfor-mance for efficient antibacterial treatments,advancing the development of antibacterial agents.

Key words

Photodynamic therapy/Antibacterial/Type-Ⅰ photosensitizers/Multidrug-resistant bacteria/Conjugated oligomers

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基金项目

国家自然科学基金(82125022)

国家自然科学基金(82072383)

国家自然科学基金(31800833)

国家自然科学基金(21977081)

国家自然科学基金(52173135)

国家自然科学基金(22207024)

浙江省自然科学基金(LZ19H180001)

Wenzhou Medical University(KYYW201901)

University of Chinese Academy of Science(WIBEZD2017001-03)

University of Chinese Academy of Science(WIUCASYJ2020001)

出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

参考文献量47

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