Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant <italic style="font-style: italic">Staphylococcus aureus</italic> Biofilm

Hui-Fang Ma; Zheng-Xin Ma; Gang-Feng Li; Yu-Tong Yang; Zhi-Heng Yang; Dan Xing; Peng Li

doi:10.1007/s10118-026-3601-1

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Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant Staphylococcus aureus Biofilm

RESEARCH ARTICLE | Updated：2026-07-01

- Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant Staphylococcus aureus Biofilm
  Enhanced Publication
- Chinese Journal of Polymer Science Vol. 44, Issue 7, Pages: 2167-2176(2026)
- Affiliations：
  
  a.Henan Institute of Flexible Electronics (HIFE) and School of Flexible Electronics (SoFE), Henan University, Zhengzhou 450046, China
  b.State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China
  c.State Key Laboratory of Flexible Electronics (LoFE) & Institute of Flexible Electronics (IFE), Shaanxi Key Laboratory of Flexible Electronics & MIIT Key Laboratory of Flexible Electronics (KLoFE), Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University (NPU), Xi’an 710072, China
- Author bio：
  
  iamgfli@mail.nwpu.edu.cn (G.F.L.)
  iampli@nwpu.edu.cn (P.L.)
- Funds：
- DOI：10.1007/s10118-026-3601-1
  CLC：
- Received：05 January 2026，
  
  Accepted：29 January 2026，
  
  Online First：09 May 2026，
  
  Published：05 July 2026
- Accepted：
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Ma, H. F.; Ma, Z. X.; Li, G. F.; Yang, Y. T.; Yang Z. H.; Xing, D.; Li, P. Microenvironment responsive polymeric nitric oxide releasing micelles for enhancing eradication of methicillin-resistant Staphylococcus aureus biofilm. Chinese J. Polym. Sci. 2026, 44, 2167–2176

Hui-Fang Ma, Zheng-Xin Ma, Gang-Feng Li, et al. Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant Staphylococcus aureus Biofilm[J]. Chinese Journal of Polymer Science, 2026, 44(7): 2167-2176. DOI: 10.1007/s10118-026-3601-1.
Ma, H. F.; Ma, Z. X.; Li, G. F.; Yang, Y. T.; Yang Z. H.; Xing, D.; Li, P. Microenvironment responsive polymeric nitric oxide releasing micelles for enhancing eradication of methicillin-resistant Staphylococcus aureus biofilm. Chinese J. Polym. Sci. 2026, 44, 2167–2176 DOI： 10.1007/s10118-026-3601-1.

Hui-Fang Ma, Zheng-Xin Ma, Gang-Feng Li, et al. Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant Staphylococcus aureus Biofilm[J]. Chinese Journal of Polymer Science, 2026, 44(7): 2167-2176. DOI: 10.1007/s10118-026-3601-1. DOI：

摘要

This study constructed polymeric micelles that released nitric oxide in response to biofilm microenvironment

effectively dispersing biofilms and significantly enhancing the bactericidal efficacy of antibiotic against methicillin-resistant

Staphylococcus aureus

biofilm.

Abstract

Biofilm infections pose a severe threat to global public health owing to their persistent and recalcitrant nature. The physical barrier formed by the biofilm impedes the penetration of antimicrobial agents

leading to a significantly reduced efficacy of conventional antibiotics. Herein

we developed a polymeric micelle system that responds to the biofilm microenvironment to release nitric oxide (NO)

which is capable of disrupting biofilms

thereby enhancing the bactericidal efficacy of antibiotics against embedded bacteria. The hydrophobic small-molecule NO donor was first conjugated to a diblock copolymer composed of

-hydroxyethyl acrylamide and

-acryloyl morpholine to yield an amphiphilic diblock copolymer. This amphiphilic copolymer then self-assembles into polymeric NO-releasing micelles (PNOM). Upon exposure to thiol-containing molecules in the reducing biofilm microenvironment

PNOM responsively released NO in a sustained manner over several days.

In vitro

studies have demonstrated that PNOM significantly potentiated the anti-biofilm efficacy of levofloxacin (Lev) against methicillin-resistant

Staphylococcus aureus

(MRSA). The combination of PNOM and Lev dispersed 85.3% of the biofilm biomass and eradicated 98.8% of the embedded bacteria. Moreover

in a murine model of implant-associated MRSA biofilm infection

PNOM was validated to enhance the antibiofilm efficacy of Lev

in vivo

achieving a bactericidal rate of 93.9 % for MRSA biofilms and significantly alleviating inflammation. In summary

we desi

gned a polymeric micelle system that triggers NO release in response to a thiol-rich biofilm microenvironment

thereby disrupting biofilm formation and enhancing the antibiofilm effect of antibiotics against MRSA. This approach represents a promising therapeutic strategy for treating stubborn biofilm-associated infections.

关键词

Keywords

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Microenvironment Responsive Polymeric Nitric Oxide Releasing Micelles for Enhancing Eradication of Methicillin-resistant Staphylococcus aureus Biofilm

DOI：10.1007/s10118-026-3601-1

摘要

Abstract

关键词

Keywords

references