Zhang Mingming, Jia Huaping, Zhuang Liang, Xu Yongjie, Zhang Ting, Gu Jianwen, He Shan, Li Dawei
The Ninth Medical Center of Chinese PLA General Hospital, 9 Anxiang Beili, Chaoyang District, Beijing 100101, China.
Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University, 11 Fucheng Road, Haidian District, Beijing 100048, China.
Colloids Surf B Biointerfaces. 2025 Mar;247:114450. doi: 10.1016/j.colsurfb.2024.114450. Epub 2024 Dec 9.
Drug-resistant bacteria infected wounds often bring high risks of delayed healing process and even death. Sonodynamic therapy (SDT) can efficiently kill drug-resistant bacteria. However, superabundant reactive oxygen species (ROS) generated during SDT inevitably trigger significant inflammatory responses, hindering tissue remodeling. Herein, we develop intelligent ultrathin high-entropy hydrotalcites (UHE-HTs)-based injectable thermal-responsive hydrogel loaded with nicotinamide mononucleotide (UHE-HTs/PFN), aiming to achieve programmed antibacterial and anti-inflammatory effects. In the early infection stage, sonosensitive UHE-HTs/PFN hydrogel simultaneously can trigger rapid production of singlet oxygen (O) under ultrasound and efficient MDR bacterial sterilization. After halting ultrasonic irradiation, oxidoreductase-mimicking catalysis and nicotinamide mononucleotide release of UHE-HTs/PFN hydrogel effectively reduce ROS levels at wound sites, dampening the NF-κB inflammatory pathway. Such inhibited NF-κB expression can not only reduce the production of pro-inflammatory cytokines and inflammatory responses, but also significantly down-regulate the pyroptosis pathways (NLRP3/ASC/Casp-1) and inhibit pyroptosis that leads to inflammation. Moreover, significantly reduced ROS levels and synergistic release of Mg reverse pro-inflammatory immune microenvironment. Both in vitro and in vivo assays demonstrate that UHE-HTs/PFN hydrogel can transform the adverse infected wound environment into a regenerative one by eradicating drug-resistant bacteria, scavenging ROS, and synergistic anti-inflammation. Therefore, this work develop an intelligent UHE-HTs/PFN hydrogel act as a "lever" that effectively achieve a balance between ROS generation and annihilation, rebuilding harmonious bactericidal and anti-inflammatory effects to remedy drug-resistant bacteria infected wound.
耐药菌感染的伤口往往会带来愈合过程延迟甚至死亡的高风险。声动力疗法（SDT）可以有效杀死耐药菌。然而，SDT过程中产生的过量活性氧（ROS）不可避免地会引发显著的炎症反应，阻碍组织重塑。在此，我们开发了一种基于智能超薄高熵水滑石（UHE-HTs）的可注射热响应水凝胶，其负载烟酰胺单核苷酸（UHE-HTs/PFN），旨在实现程序化的抗菌和抗炎效果。在感染早期，对超声敏感的UHE-HTs/PFN水凝胶在超声作用下可同时触发单线态氧（¹O₂）的快速产生和高效的多重耐药菌杀菌作用。停止超声照射后，UHE-HTs/PFN水凝胶的氧化还原酶模拟催化和烟酰胺单核苷酸释放可有效降低伤口部位的ROS水平，抑制NF-κB炎症通路。这种NF-κB表达的抑制不仅可以减少促炎细胞因子的产生和炎症反应，还能显著下调焦亡途径（NLRP3/ASC/Casp-1）并抑制导致炎症的焦亡。此外，显著降低的ROS水平和Mg的协同释放可逆转促炎免疫微环境。体外和体内实验均表明，UHE-HTs/PFN水凝胶可通过根除耐药菌、清除ROS和协同抗炎将不利的感染伤口环境转变为再生环境。因此，这项工作开发了一种智能UHE-HTs/PFN水凝胶，作为一个“杠杆”，有效地实现ROS产生与消除之间的平衡，重建和谐的杀菌和抗炎效果，以治疗耐药菌感染的伤口。
