Bioorthogonal Polymer Nanozymes for Effective Treatment of Bacterial Wound Biofilm Infections

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Publication Details

Journal
ACS Applied Materials & Interfaces
Published
2026-09-09
DOI
https://doi.org/10.1021/acsami.6c12077
Primary Topic
Antimicrobial agents and applications
Type
article
Field-Weighted Citation Impact
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article

Bioorthogonal Polymer Nanozymes for Effective Treatment of Bacterial Wound Biofilm Infections

William Ndugire, Nourina Nasim, Yağız Anıl Çiçek, Maged Abdelaziz et al.
ACS Applied Materials & Interfaces
Antimicrobial agents and applications
article

Bioorthogonal Polymer Nanozymes for Effective Treatment of Bacterial Wound Biofilm Infections

William Ndugire, Nourina Nasim, Yağız Anıl Çiçek, Maged Abdelaziz, Junwhee Yang, Vincent M. Rotello, Muhammad Aamir Hassan, Joe Truong, Mathangi Shrikanth, Cristina-Maria Hirschbiegel
article en

Abstract

Multidrug-resistant (MDR) bacterial infections are a rapidly emerging healthcare crisis. The challenge of MDR bacteria is further exacerbated through biofilm formation that limits effective drug penetration and hinders the ability of the host immune system to clear the infection. Cationic polymer nanoparticles carrying bioorthogonal transition-metal catalysts (polyzymes) can penetrate bacterial biofilms and locally catalyze the uncaging of antimicrobial drug derivatives, acting as an in situ bioorthogonal "drug factory". Polyzymes were designed and fabricated using an amphiphilic polymer nanoscaffold and iron(III) tetraphenyl porphyrin as the catalyst. The polyzyme bioorthogonally uncaged an azide-protected prodrug of the antimicrobial drug moxifloxacin. The efficacy of this approach was tested in vitro against an in vitro Escherichia coli (E. coli) biofilm, resulting in a ∼3.5-log10 colony-forming units (CFU/mL) reduction of bacterial load (99.99%). The polyzyme was subsequently incorporated into a thermoresponsive Poloxamer 407 hydrogel to create a wound dressing, and the localized activation of pro-moxifloxacin was tested in an in vivo E. coli wound biofilm model. The polyzyme-mediated localized activation of the prodrug was highly effective, resulting in significantly more bacterial killing compared to the free drug moxifloxacin. These results demonstrate the therapeutic potential of bioorthogonal polyzymes for treating wound biofilm infections, with enhanced local activity and improved treatment outcomes compared to standard clinical treatment methods.

ACS Applied Materials & Interfaces
University of Massachusetts Amherst (US)
Good health and well-being
Openalex Percentile: Top 20%
Antimicrobial agents and applications
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