Antibacterial photodynamic therapy (aPDT) has emerged as a promising strategy for treating periodontitis. However, the weak binding of most photosensitizers to bacteria and the hypoxic environment of periodontal pockets severely hamper the therapeutic efficacy. Herein, two novel oxygen-independent photosensitizers are developed by introducing selenophene into viologens and modifying with hexane chains (HASeV) or quaternary ammonium chains (QASeV), which improve the adsorption to bacteria through anchoring to the negatively charged cell membrane. Notably, QASeV binds only to the bacterial surface of and due to electrostatic binding, but HASeV can insert into their membrane by strong hydrophobic interactions. Therefore, HASeV exhibits superior antimicrobial activity and more pronounced plaque biofilm disruption than QASeV when combined with light irradiation (MVL-210 photoreactor, 350–600 nm, 50 mW/cm), and a better effect on reducing the diversity and restoring the structure of subgingival flora in periodontitis rat model was found through 16S rRNA gene sequencing analysis. The histological and Micro-CT analyses reveal that HASeV-based aPDT has a better therapeutic effect in reducing periodontal tissue inflammation and alveolar bone resorption. This work provides a new strategy for the development of viologen-based photosensitizers, which may be a favorable candidate for the aPDT against periodontitis.

中文翻译：

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膜锚定硒吩紫精通过恢复龈下菌群和减轻炎症来抗菌光动力治疗牙周炎

抗菌光动力疗法（aPDT）已成为治疗牙周炎的一种有前途的策略。然而，大多数光敏剂与细菌的结合较弱，牙周袋的缺氧环境严重影响了治疗效果。在此，通过将硒酚引入紫精中并用己烷链（HASeV）或季铵链（QASeV）进行修饰，开发了两种新型的不依赖于氧的光敏剂，通过锚定到带负电的细胞膜来提高对细菌的吸附。值得注意的是，QASeV 仅通过静电结合与细菌表面结合，但 HASeV 可以通过强疏水相互作用插入细菌膜。因此，当与光照射（MVL-210光反应器，350-600 nm，50 mW/cm）结合时，HASeV比QASeV表现出更优异的抗菌活性和更明显的菌斑生物膜破坏作用，并且对降低菌斑多样性和恢复结构有更好的效果。通过16S rRNA基因测序分析发现牙周炎大鼠模型龈下菌群。组织学和Mi​​cro-CT分析表明，基于HASeV的aPDT在减少牙周组织炎症和牙槽骨吸收方面具有更好的治疗效果。这项工作为开发基于紫罗碱的光敏剂提供了一种新策略，它可能是治疗牙周炎的 aPDT 的有利候选者。