Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague–Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.

中文翻译：

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基于细菌细胞穿透性光敏剂的多功能纳米系统通过光动力和抗生素疗法相结合对抗牙周炎

光动力疗法（PDT）是一种涉及光敏剂，光和分子氧的新兴方法，已显示出对抗牙周炎的希望。但是，PDT并非总能获得理想的治疗效果，因为某些光敏剂具有很强的疏水性，并且很难被牙周病原菌有效吸收。在这里，疏水性光敏剂二氢卟酚e6（Ce6）通过与TAT肽（一种穿透细胞的阳离子肽）偶联进行了亲水修饰，以改善其溶解度并通过促进其与带负电的细胞壁的相互作用和穿透细胞的能力来增强其细菌吸附力。膜。使用获得的TAT-Ce6共轭物（TAT-Ce6）制备自组装的纳米颗粒（NPs），以装载临床上使用的抗生素替硝唑（TDZ），因此希望通过将PDT和抗生素疗法相结合来达到协同的抗牙周炎的作用。与游离的Ce6相比，TAT-Ce6纳米颗粒（TAT-Ce6 NPs）极大地增强了对牙周病原菌的吸附和渗透能力，并且在牙周病原菌和单核巨噬细胞中的PDT效率也显着提高。在635 nm激光照射下，载有TDZ的TAT-Ce6（TAT-Ce6 / TDZ）NP在PDT和抗生素治疗方面发挥了显着的协同抗牙周炎作用，这反映出体外有效地杀死了牙周病原菌并减少了牙槽骨的吸收Sprague-Dawley大鼠牙周炎模型。共，