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Flexible electrostatic hydrogels from marine organism for nitric oxide-enhanced photodynamic therapy against multidrug-resistant bacterial infection

海洋生物源静电水凝胶实现一氧化氮增强光动力治疗以对抗多药耐药菌感染

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Abstract

The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drug-resistant bacteria. Thus, the development of novel antibacterial materials is attracting increasing attention. Here, a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide (NO)-releasing nitrated chitosan (CSNO) and mesotetra(4-carboxyphenyl)porphine (TCPP) with salmon sperm DNA (ssDNA) solution. When cultured with gram-negative bacteria under solar simulator irradiation, TCPP-CSNOm-ssDNAn hydrogels released reactive oxygen species (ROS) and NO to produce peroxynitrite ions (ONOO−). ONOO− is efficient at killing bacteria, thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria. The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drug-resistant bacteria, making them a promising candidate for clinical applications. A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.

摘要

在治疗微生物感染疾病方面滥用抗生素提高了耐药菌的致病率. 本研究提出了一种利用硝化壳聚糖与鱼精DNA包裹光敏剂构建静电水凝胶(TCPP-CSNOm-ssDNAn)的策略. 在模拟太阳光的照射下, 水凝胶TCPP-CSNOm-ssDNAn释放一氧化氮与活性氧物质, 进而形成具有强氧化活性的过氧亚硝酸盐离子(OONO−), 实现了高效协同杀灭多药耐药革兰氏阴性菌的作用, 改善了单一的光动力治疗对革兰氏阴性菌效果不佳的现状. 在用于治疗由多药耐药的铜绿假单胞菌引起的皮肤感染时, 水凝胶TCPP-CSNO2-ssDNA1在体内表现出有效的抗菌作用, 同时具有生物安全性, 这使其在抗感染伤口敷料领域具有巨大的应用潜力.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2021YFB3800900), the National Natural Science Foundation of China (22122501, 21875014 and 52073013), and Beijing Outstanding Young Scientist Program (BJJWZYJH01201910010024).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education) and Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    Yujie Sun  (孙玉洁), Rong-Lai Wen  (闻荣来), Dan Yu  (余丹), Yiwen Zhu  (朱艺文), Liang Zheng  (郑良), Haoran Wang  (王浩然), Bingran Yu  (俞丙然) & Fu-Jian Xu  (徐福建)

  2. School of Materials Science and Engineering, Zhejiang Sci-Tech University, Xiasha Higher Education Zone, Hangzhou, 310018, China

    Xiangdong Liu  (刘向东)

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  1. Yujie Sun  (孙玉洁)
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Contributions

Xu FJ and Yu B directed the research. Sun Y and Wen RL contributed equally to the preparation and characterization of hydrogels. Yu D, Zhu Y and Zheng L helped to accomplish biocompatibility and in vivo tests. Wang H helped to analyze the data. Liu X offered experimental materials.

Corresponding authors

Correspondence to Bingran Yu  (俞丙然) or Fu-Jian Xu  (徐福建).

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Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary information

Experimental details and supporting data are available in the online version of the paper.

Yujie Sun received her BSc degree from Yanshan University in 2018. She is currently a doctor student under the supervision of Prof. Fu-Jian Xu and Prof. Bingran Yu at Beijing University of Chemical Technology. Her research interests focus on photodynamic antibacterial polymers and cationic polymers for biomacromolecule delivery.

Rong-Lai Wen received his master’s degree from Beijing University of Chemical Technology in 2021. His research interests focus on polysaccharide-based biomass hydrogels for photodynamic antibacterial effect.

Bingran Yu is currently a professor at Beijing University of Chemical Technology. He obtained his PhD degree in inorganic chemistry from Lanzhou University in 2013 and then joined Beijing University of Chemical Technology. Prof. Yu has contributed significantly to the field of design, construction, and application of drug/gene delivery vectors and novel antibacterial polymers.

Fu-Jian Xu is currently a professor at Beijing University of Chemical Technology. He obtained his PhD degree in biomolecular engineering in 2006 from the National University of Singapore. He joined Beijing University of Chemical Technology, China as a professor in 2009. He was recipient of the National Science Foundation for Distinguished Young Scholars (NSFC, 2013) and Cheung Kong Distinguished Professor (Ministry of Education of China, 2014). His research interests focus on functional bio-macromolecules.

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Flexible electrostatic hydrogels from marine organism for nitric oxide-enhanced photodynamic therapy against multidrug-resistant bacterial infection

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Sun, Y., Wen, RL., Yu, D. et al. Flexible electrostatic hydrogels from marine organism for nitric oxide-enhanced photodynamic therapy against multidrug-resistant bacterial infection. Sci. China Mater. 65, 2850–2860 (2022). https://doi.org/10.1007/s40843-022-2024-6

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