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    Nitric Oxide-Releasing Therapeutics for Treating Bacterial Infections: Anatomical Targeting and Therapeutic Design
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    • Courtney R. Johnson
      Courtney R. Johnson
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Tsian D. Ramrattan
      Tsian D. Ramrattan
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Mikaylin E. Nogler
      Mikaylin E. Nogler
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Kacey N. Durkin
      Kacey N. Durkin
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Joseph J. Metiva
      Joseph J. Metiva
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Sarah G. Nagy
      Sarah G. Nagy
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Mark H. Schoenfisch*
      Mark H. Schoenfisch
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      *Email: [email protected]
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    ACS Infectious Diseases

    Cite this: ACS Infect. Dis. 2026, XXXX, XXX, XXX-XXX
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    https://doi.org/10.1021/acsinfecdis.5c01153
    Published April 8, 2026
    © 2026 American Chemical Society

    Abstract

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    Targeted therapeutic delivery for treating bacterial infections remains underutilized in most pharmaceutical interventions. Existing therapeutics (i.e., antibiotics) are often systematically administered despite the presence of localized infection, leading to both off-target toxicity and suboptimal bacterial clearance with limited efficacy against biofilms. The overuse of antibiotics has resulted in increased antimicrobial resistance, creating a need for alternative interventions that are unlikely to confer resistance. Nitric oxide (NO), an endogenous mediator produced by macrophages and other immune cells in response to infection, elicits broad spectrum antibacterial and antibiofilm activity. The use of exogenous NO donors, alone or as conjugated ligands to macromolecular scaffolds, has proven effective in treating anatomical targets, including dermal wounds, dental infections, and pulmonary conditions, in a localized manner. In this perspective, we provide an overview of the recent advancements in NO-releasing biomaterials, highlighting design strategy and antimicrobial action across diverse anatomical sites.

    © 2026 American Chemical Society

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    ACS Infectious Diseases

    Cite this: ACS Infect. Dis. 2026, XXXX, XXX, XXX-XXX
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsinfecdis.5c01153
    Published April 8, 2026
    © 2026 American Chemical Society

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