Qi Ye, Ren Shuangsong, Ou Xiaolong, Li Pisong, Wu Han, Che Ying, Wang Xinyi
Research Institute of Biomedical and Advanced Materials, College of Life and Health, Dalian University, 10 Xuefu Street, Dalian, Liaoning, 116622, China.
Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, 193 Lianhe Road, Dalian, Liaoning, 116011, China.
Biomaterials. 2025 Oct;321:123338. doi: 10.1016/j.biomaterials.2025.123338. Epub 2025 Apr 10.
Antibiotic-resistant bacterial infections present a growing global health challenge, requiring innovative therapeutic solutions to overcome current limitations. We introduce boron-integrated bismuth oxide (B-BiO) nanosheets with an asymmetrically distributed electronic structure for ultrasound-activated synergistic sonothermal and catalytic therapy. Boron incorporation enhances local electron density distribution, optimizing charge separation and significantly improving sonothermal and catalytic efficiency, as validated by density functional theory calculations. These nanosheets exhibit dual functionality, effectively generating localized heat and reactive oxygen species (ROS) under ultrasound, leading to 99.999 % antibacterial efficacy against multidrug-resistant pathogens by disrupting bacterial membranes, as demonstrated through all-atom simulations and in vitro experiments. The simulations further reveal that sonothermal conversion effects enhance bacterial membrane fluidity and induce structural defects, amplifying ROS-induced oxidative damage and membrane destabilization. In vivo, B-BiO nanosheets accelerate wound healing in methicillin-resistant Staphylococcus aureus (MRSA)-infected murine models, achieving 99.8 % closure by day 14 by reducing inflammation and promoting angiogenesis and tissue regeneration. Transcriptomic analysis highlights the activation of extracellular matrix remodeling, angiogenesis, and autophagy pathways, underscoring the nanosheets' therapeutic potential. This study establishes ultrasound-activated B-BiO nanosheets as a novel nanotherapeutic platform, leveraging asymmetric electron distribution to synergistically combat drug-resistant infections and promote effective wound healing.
抗生素耐药性细菌感染给全球卫生带来了日益严峻的挑战，需要创新的治疗方案来克服当前的局限性。我们引入了具有不对称分布电子结构的硼集成氧化铋（B-BiO）纳米片，用于超声激活的协同声热和催化治疗。密度泛函理论计算验证，硼的掺入增强了局部电子密度分布，优化了电荷分离并显著提高了声热和催化效率。这些纳米片具有双重功能，在超声作用下能有效产生局部热量和活性氧（ROS），通过破坏细菌膜对多重耐药病原体产生99.999%的抗菌效果，全原子模拟和体外实验证明了这一点。模拟进一步揭示，声热转换效应增强了细菌膜的流动性并诱导结构缺陷，放大了ROS诱导的氧化损伤和膜不稳定。在体内，B-BiO纳米片加速了耐甲氧西林金黄色葡萄球菌（MRSA）感染小鼠模型的伤口愈合，通过减轻炎症、促进血管生成和组织再生，在第14天实现了99.8%的伤口闭合。转录组分析突出了细胞外基质重塑、血管生成和自噬途径的激活，强调了纳米片的治疗潜力。本研究将超声激活的B-BiO纳米片确立为一种新型纳米治疗平台，利用不对称电子分布协同对抗耐药感染并促进有效的伤口愈合。
