Issue 12, 2023

Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections

Abstract

Treatment of wound biofilm infections faces challenges from both pathogens and uncontrolled host immune response. Treating both issues through a single vector would provide enhanced wound healing. Here, we report the use of a potent cationic antimicrobial polymer to generate siRNA polyplexes for dual-mode treatment of wound biofilms in vivo. These polyplexes act both as an antibiofilm agent and a delivery vehicle for siRNA for the knockdown of biofilm-associated pro-inflammatory MMP9 in host macrophages. The resulting polyplexes were effective in vitro, eradicating MRSA biofilms and efficiently delivering siRNA to macrophages in vitro with concomitant knockdown of MMP9. These polyplexes were likewise effective in an in vivo murine wound biofilm model, significantly reducing bacterial load in the wound (∼99% bacterial clearance) and reducing MMP9 expression by 80% (qRT-PCR). This combination therapeutic strategy dramatically reduced wound purulence and significantly expedited wound healing. Taken together, these polyplexes provide an effective and translatable strategy for managing biofilm-infected wounds.

Graphical abstract: Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections

Supplementary files

Article information

Article type
Communication
Submitted
15 Maw 2023
Accepted
29 Ndz 2023
First published
29 Ndz 2023

Mater. Horiz., 2023,10, 5500-5507

Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections

T. Jeon, J. M. V. Makabenta, J. Park, A. Nabawy, Y. A. Cicek, S. S. Mirza, J. Welton, M. A. Hassan, R. Huang, J. Mager and V. M. Rotello, Mater. Horiz., 2023, 10, 5500 DOI: 10.1039/D3MH01108A

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