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精氨酸丰富的两亲性树枝状肽作为一种多功能的 NO 供体,用于协同治疗细菌感染和促进伤口愈合的 NO/光动力治疗。

L-Arg-Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing.

机构信息

College of Materials Science and Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China.

School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, P. R. China.

出版信息

Small. 2021 Aug;17(32):e2101495. doi: 10.1002/smll.202101495. Epub 2021 Jul 2.

Abstract

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H O generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen ( O ) production. The combination of O and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

摘要

迫切需要开发替代策略,以有效治疗皮下脓肿,而无需大量使用抗生素和手术干预。本文报道了一种基于光动力(PDT)和 NO 气体治疗的新型协同抗菌策略,其中开发了一种基于 PDT 驱动的 NO 可控产生系统(Ce6@Arg-ADP),以富含 l-Arg 的两亲性树枝状肽(Arg-ADP)为载体。该载体不仅表现出优异的细菌结合和生物膜穿透性能,而且还可以作为多功能的 NO 供体。在有效穿透生物膜内部后,Ce6@Arg-ADP 可以通过利用 PDT 产生的 H2O2 将 Arg-ADP 氧化为 NO 和 l-瓜氨酸来快速产生大量的 NO,而不会影响单线态氧(1O2)的产生。1O2 和 NO 的反应副产物的组合提供了显著的协同抗菌和生物膜清除效果。重要的是,在从脓肿部位有效消除所有细菌后,Arg-ADP 可以进一步产生微量的 NO,以促进伤口组织的血管生成和上皮化,从而显著促进伤口愈合。总之,本研究清楚地表明 Arg-ADP 是一种多功能的 NO 供体,PDT 和 NO 的组合代表了一种有效治疗皮下脓肿的有前途的策略。

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