Ma Guangrong, Cheng Ke, Wang Xue, Zeng Yiqing, Hu Chenlu, He Luying, Shi Zhan, Lin Hengwei, Zhang Tao, Sun Shan, Huang Pintong
Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, PR China; Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, PR China.
International Joint Research Center for Photo-Responsive Molecules and Materials School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu, 214122, PR China.
Biomaterials. 2025 Jul;318:123145. doi: 10.1016/j.biomaterials.2025.123145. Epub 2025 Jan 25.
Diabetic wounds present significant treatment challenges due to their complex microenvironment, marked by persistent inflammation from bacterial infections, hypoxia caused by diabetic microangiopathy, and biofilm colonization. Sonodynamic therapy (SDT) offers potential for treating such wounds by targeting deep tissues with antibacterial effects, but its efficacy is limited by hypoxic conditions and biofilm barriers. To overcome these obstacles, we developed a novel approach using oxygen-carrying microbubbles loaded with Mn-doped carbon dots (MnCDs@OMBs) to enhance SDT and disrupt biofilms. Through precursor screening and design, MnCDs are engineered to exhibit tailored properties of sonodynamic activity and enzyme-like catalytic capabilities. This system provides a dual oxygen supply for amplifying the SDT effects: MnCDs, serving as a sonosensitizer, also chemically convert excess HO at infection sites into oxygen, while the OMBs physically release oxygen through ultrasound-induced cavitation. The cavitation effect also disrupts biofilms, improving the delivery of sonosensitizers and boosting SDT efficacy. In a diabetic wound model, this strategy downregulated TLR, NF-κB, and TNF inflammatory pathways, reduced pro-inflammatory factor secretion, promoted angiogenesis, and accelerated wound healing, thereby acting as a promising treatment approach for diabetic wound healing.
糖尿病伤口由于其复杂的微环境而带来了重大的治疗挑战，其特征包括细菌感染引起的持续炎症、糖尿病微血管病变导致的缺氧以及生物膜定植。声动力疗法（SDT）通过靶向深部组织发挥抗菌作用，为治疗此类伤口提供了潜力，但其疗效受到缺氧条件和生物膜屏障的限制。为了克服这些障碍，我们开发了一种新方法，使用负载锰掺杂碳点的载氧微泡（MnCDs@OMBs）来增强声动力疗法并破坏生物膜。通过前体筛选和设计，对锰掺杂碳点进行工程改造，使其具有定制的声动力活性和类酶催化能力。该系统为放大声动力疗法的效果提供了双重氧气供应：锰掺杂碳点作为声敏剂，还能将感染部位多余的羟基自由基化学转化为氧气，而微泡则通过超声诱导的空化作用物理释放氧气。空化效应还能破坏生物膜，改善声敏剂的递送并提高声动力疗法的疗效。在糖尿病伤口模型中，该策略下调了Toll样受体（TLR）、核因子κB（NF-κB）和肿瘤坏死因子（TNF）炎症通路，减少促炎因子分泌，促进血管生成并加速伤口愈合，从而成为一种有前景的糖尿病伤口愈合治疗方法。
