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用于牙周炎治疗的具有抗菌和中性粒细胞胞外陷阱降解双功能特性的双纳米酶负载核壳微针贴片。

Dual nanozymes-loaded core-shell microneedle patches with antibacterial and NETs-degradation bifunctional properties for periodontitis treatment.

作者信息

Shan Yue, Zhong Jiahui, Sun Qiang, Gao Weijin, Zhang Chenyin, Chen Hongyu, Zhou Jiaqi, Ye Ziqiang, Chen Qianming, Mao Zhengwei, Wu Mengjie

机构信息

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

出版信息

Bioact Mater. 2025 Jul 9;53:161-177. doi: 10.1016/j.bioactmat.2025.07.003. eCollection 2025 Nov.

Abstract

Periodontitis, a chronic inflammatory disease affecting over one billion people worldwide, is characterized by bacterial infections and hyperactive immune responses. Recent studies have revealed that the formation of neutrophil extracellular traps (NETs) contributes significantly to periodontal tissue destruction, and NETs degradation plays a critical role in periodontitis treatment. Current treatments, including mechanical debridement and systemic antibiotics, face limitations such as antibiotic resistance and insufficient local efficacy. To integrate antibacterial and NETs-elimination strategies, the authors propose a novel therapeutic approach using bifunctional core-shell microneedles (MNs) that deliver two types of nanozymes: a peroxidase (POD)-like palladium (Pd) nanozyme in the inner core layer and a DNase-like dendritic mesoporous silica nanoparticles (DMSN)-cerium (Ce) nanozyme in the outer layer. The Pd/Ce MNs are designed to facilitate the rapid release of Pd for bacterial eradication and the sustained release of DMSN-Ce for NETs degradation. This study details the synthesis and characterization of two nanozymes and core-shell structured MNs, followed by evaluations of their catalytic activities, biocompatibility, antibacterial efficacy and NETs-cleavage ability. testing using a rat model of periodontitis demonstrates significant improvements in bacterial clearance, inflammation reduction, and alveolar bone preservation. In conclusion, these findings suggest that Pd/Ce MNs with superior antibacterial and NETs-hydrolyzing properties represent a promising therapeutic strategy for the management of periodontitis.

摘要

牙周炎是一种影响全球超过10亿人的慢性炎症性疾病,其特征为细菌感染和免疫反应亢进。最近的研究表明,中性粒细胞胞外陷阱(NETs)的形成对牙周组织破坏有显著贡献,而NETs降解在牙周炎治疗中起关键作用。目前的治疗方法,包括机械清创和全身使用抗生素,面临着诸如抗生素耐药性和局部疗效不足等局限性。为了整合抗菌和消除NETs的策略,作者提出了一种使用双功能核壳微针(MNs)的新型治疗方法,该微针可递送两种类型的纳米酶:内核层中的类过氧化物酶(POD)钯(Pd)纳米酶和外层中的类脱氧核糖核酸酶树枝状介孔二氧化硅纳米颗粒(DMSN)-铈(Ce)纳米酶。设计Pd/Ce MNs是为了促进Pd的快速释放以根除细菌,并使DMSN-Ce持续释放以降解NETs。本研究详细介绍了两种纳米酶和核壳结构MNs的合成与表征,随后评估了它们的催化活性、生物相容性、抗菌功效和NETs切割能力。使用大鼠牙周炎模型进行的测试表明,在细菌清除、炎症减轻和牙槽骨保存方面有显著改善。总之,这些发现表明,具有卓越抗菌和NETs水解特性的Pd/Ce MNs代表了一种治疗牙周炎的有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4334/12274864/93dff1d4e51d/ga1.jpg

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