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The ascendant danger of bacterial infections has resulted in an urgent requirement for developing new antibacterial approaches. Recently, nitric oxide (NO) has shown a broad-spectrum antimicrobial activity while avoiding resistance. However, achieving effective NO-based antibacterial therapies remains challenging, mired by the safety concerns of NO donor, residual toxicity by the ingredients, or complicated procedures. Herein, a self-activated NO-releasing hydrogel depot is fabricated by Ca2+-crosslinked sodium alginate doped with CaO2 nanoparticles, L-arginine, and oxidized mesoporous carbon nanoparticles (OMCN) for photothermal enhanced bacteria killing. The locally concentrated H2O2, generated from the reaction of CaO2 nanoparticles and water, could oxidize L-arginine to release NO. Meanwhile, benefiting from the remarkable photothermal effect of OMCN, the hybrid hydrogel possesses a synergistic sterilization behavior in combating both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria in vitro. Moreover, the dual therapeutic hydrogel displays high efficiency in treatment of bacteria-infected mice with back wound model while showing no distinct toxicity. In addition, the restricted environment of hydrogel makes it easy to remove all the components from the infected wound, alleviating possible side effects from exogenous H2O2. As such, the designed NO-synergistic photothermal hydrogel provides a promising strategy for treating bacterial infections.


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A self-activated NO-releasing hydrogel depot for photothermal enhanced sterilization

Show Author's information Shen Zhang1Kelei Guan3Yaoxin Zhang1Junqing Zhang1Hongyu Fu4Ting Wu2Dilan Ouyang2Chaoqun Liu1( )Qiang Wu1( )Zhaowei Chen2( )
School of Pharmacy, Henan University, Kaifeng 475004, China
Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou 350108, China
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Henan University School of Stomatology, Kaifeng 475004, China

Abstract

The ascendant danger of bacterial infections has resulted in an urgent requirement for developing new antibacterial approaches. Recently, nitric oxide (NO) has shown a broad-spectrum antimicrobial activity while avoiding resistance. However, achieving effective NO-based antibacterial therapies remains challenging, mired by the safety concerns of NO donor, residual toxicity by the ingredients, or complicated procedures. Herein, a self-activated NO-releasing hydrogel depot is fabricated by Ca2+-crosslinked sodium alginate doped with CaO2 nanoparticles, L-arginine, and oxidized mesoporous carbon nanoparticles (OMCN) for photothermal enhanced bacteria killing. The locally concentrated H2O2, generated from the reaction of CaO2 nanoparticles and water, could oxidize L-arginine to release NO. Meanwhile, benefiting from the remarkable photothermal effect of OMCN, the hybrid hydrogel possesses a synergistic sterilization behavior in combating both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria in vitro. Moreover, the dual therapeutic hydrogel displays high efficiency in treatment of bacteria-infected mice with back wound model while showing no distinct toxicity. In addition, the restricted environment of hydrogel makes it easy to remove all the components from the infected wound, alleviating possible side effects from exogenous H2O2. As such, the designed NO-synergistic photothermal hydrogel provides a promising strategy for treating bacterial infections.

Keywords: hydrogel, photothermal, antibacterial, nitric oxide, bacterial infections

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Publication history
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Acknowledgements

Publication history

Received: 20 September 2022
Revised: 20 October 2022
Accepted: 23 October 2022
Published: 31 December 2022
Issue date: April 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

Financial support was provided by the National Key Research and Development Program of China (No. 2020YFA0210800), the Key Technologies R & D Program of Henan (No. 212102310231), the Academic Key Research Projects of Henan (Nos. 21A430006 and 22A310010), the Major Project of Science and Technology of Fujian Province (No. 2020HZ06006), and the National Natural Science Foundation of China (Nos. 22277011 and 22107019).

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