Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections.
Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections.
复制标题
抗菌聚合物-siRNA 复合物作为治疗伤口生物膜感染的双模式平台。
DOI：
10.1039/d3mh01108a
复制
发表时间：
2023
影响因子：
13.3
通讯作者：
Rotello,VincentM
中科院分区：
文献类型：
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作者：
Jeon,Taewon;Makabenta,JessaMarieV;Park,Jungmi;Nabawy,Ahmed;Cicek,YagizAnil;Mirza,SarahS;Welton,Janelle;Hassan,MuhammadAamir;Huang,Rui;Mager,Jesse;Rotello,VincentM
伤口生物膜感染的治疗面临来自病原体和不受控制的宿主免疫应答的挑战。通过单一载体治疗这两个问题将提供增强的伤口愈合。在这里，我们报告了使用一种有效的阳离子抗菌聚合物产生siRNA复合物的双模式治疗体内伤口生物膜。这些聚合复合物既作为生物膜试剂又作为siRNA的递送载体，用于敲低宿主巨噬细胞中生物膜相关的促炎性MMP 9。所得到的复合物在体外是有效的，消除MRSA生物膜，并在体外有效地将siRNA递送至巨噬细胞，同时敲低MMP 9。这些复合物在体内鼠伤口生物膜模型中同样有效，显著降低伤口中的细菌负荷（约99%细菌清除率）并使MMP 9表达降低80%（qRT-PCR）。这种联合治疗策略显著减少了伤口化脓并显著加速了伤口愈合。总之，这些复合物为管理生物膜感染的伤口提供了有效且可转化的策略。
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.