박정미 (University of Massachusetts Amherst) | 한빛사논문 > 한빛사

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조회424

박정미Jungmi Park

University of Massachusetts Amherst

Mater. Horizons, Oct 10 2023, | https://doi.org/10.1039/d3mh01108a Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections

Taewon Jeon,^‡a Jessa Marie V. Makabenta,^‡b Jungmi Park,^‡b Ahmed Nabawy,^b Yagiz Anil Cicek,^b Sarah S. Mirza,c Janelle Welton,^c Muhammad Aamir Hassan,^b Rui Huang,^b Jesse Magerc and Vincent M. Rotello^*ab

^aMolecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, Massachusetts, USA

^bDepartment of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts, USA

^cDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 N Pleasant Street, Amherst, Massachusetts, USA

^‡These authors contributed equally to this work.

^*Corresponding author : Vincent M. Rotello

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.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-11-15)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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