Developing HMME-Conjugated NIR-II Activated Carbon Dots Nanospray for the Treatment of MRSA Biofilm Infections in Diabetic Wound via PTT/CDT/SDT

en This link goes to a English section zh This link goes to a Chinese section Diabetic wound infections are a common complication of diabetes, which severely impact patients' quality of life. Effective treatment of diabetic wound infections remains one major challenge in the clinic, partially due to the formation of bacterial biofilm and antibiotic resistance. It is imperative to develop non-antibiotic-dependent strategies to efficiently eradicate biofilm infections in diabetic wounds. In this work, an innovative nanospray (CDs-HM) was successfully prepared by linking one acoustic sensitizer (hematoporphyrin monomethyl ether, HMME) to CDs fabricated with hemin, nickel(II) chloride, and polymer ethylene imine. CDs-HM exhibited catalase-enhanced sonodynamic properties and photothermal-enhanced chemodynamic properties. In vitro experiments and transcriptomic analysis demonstrated that CDs-HM successfully killed the bacteria and destroyed bacterial biofilm by disrupting bacterial cell membrane integrity, inducing oxidative stress, and inhibiting ATP production through synergistic photothermal therapy/chemodynamic therapy/sonodynamic therapy (PTT/CDT/SDT) effects. In the diabetic wound infection mouse model, CDs-HM remarkably eradicated MRSA biofilm, reduced inflammation levels, and promoted angiogenesis/collagen deposition so as to accelerate wound healing. It is noteworthy that CDs-HM displayed superior bacteria killing and wound healing effects compared with conventional vancomycin and nanosilver dressing interventions. The practicality and efficiency of CDs-HM endowed it with broad clinical translation prospects. It paved the way for developing novel strategies for combating diabetic wound infections. 摘要 en This link goes to a English section zh This link goes to a Chinese section 糖尿病伤口感染是糖尿病的常见并发症,严重影响患者的生活质量。由于细菌生物膜的形成和抗生素耐药性问题,糖尿病伤口感染的有效治疗仍是临床面临的一大挑战。因此,亟待开发非抗生素依赖的新策略以高效清除糖尿病伤口的生物膜感染。本研究通过将声敏剂(血卟啉单甲醚,HMME)与由氯化血红素、氯化镍和聚乙烯亚胺制备的碳点相偶联,成功构建了一种新型纳米喷雾(CDs-HM)。CDs-HM表现出过氧化氢酶增强的声动力学性能与光热增强的化学动力学性能。体外实验及转录组学分析表明,通过协同的光热/化学动力学/声动力学治疗,CDs-HM可破坏细菌细胞膜的完整性、诱导氧化应激并抑制ATP的生成,从而有效杀灭细菌并破坏其生物膜。在糖尿病伤口感染小鼠模型中,CDs-HM能显著清除耐甲氧西林金黄色葡萄球菌生物膜、降低炎症水平并促进血管生成和胶原沉积,进而加速伤口愈合。值得注意的是,与临床上常用的万古霉素和纳米银敷料联合治疗措施相比,CDs-HM展现出更优异的杀菌及促伤口愈合效果。CDs-HM展示出较强的实用性,使其具备了广阔的临床转化前景,也为开发糖尿病伤口感染治疗的新型策略奠定了基础。