Yang Kaili, Dong Heng, Xiu Weijun, Yuwen Lihui, Mou Yongbin, Yin Zhaowei, Liang Bin, Wang Lianhui
State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China.
ACS Appl Mater Interfaces. 2023 Apr 19;15(15):18720-18733. doi: 10.1021/acsami.3c01928. Epub 2023 Apr 5.
Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow CuMoS nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.
由于细菌生物膜诱导的抗生素耐受性和免疫反应受损，植入物感染难以通过传统抗生素疗法治愈。为了有效治疗植入物感染，治疗剂需要在生物膜消除过程中杀死细菌并调节免疫细胞的炎症反应。在此，制备了具有pH响应酶样活性的多功能智能空心CuMoS纳米球（H-CMS NSs），用于自适应消除生物膜并调节植入物感染中巨噬细胞的炎症。在生物膜感染期间，植入物周围的组织微环境呈酸性。具有氧化酶（OXD）/过氧化物酶（POD）样活性的H-CMS NSs可以催化活性氧（ROS）生成，直接杀死细菌并将巨噬细胞极化为促炎表型。此外，在超声（US）照射下，H-CMS NSs的POD样活性和抗菌性能可以进一步增强。生物膜消除后，植入物周围的组织微环境从酸性转变为中性。H-CMS NSs表现出过氧化氢酶（CAT）样活性并消除过量的ROS，这将巨噬细胞极化为抗炎表型并促进感染组织的愈合。这项工作提供了一种智能纳米酶，通过在植入物感染的不同治疗阶段根据不同的病理微环境调节ROS的产生/消除，对生物膜活性和免疫反应进行自适应调节。
