A Multifunctional Nanosystem Based on Bacterial Cell-Penetrating Photosensitizer for Fighting Periodontitis Via Combining Photodynamic and Antibiotic Therapies
A Multifunctional Nanosystem Based on Bacterial Cell-Penetrating Photosensitizer for Fighting Periodontitis Via Combining Photodynamic and Antibiotic Therapies
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DOI：
10.1021/acsbiomaterials.0c01638
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发表时间：
2021-01-07
影响因子：
5.8
通讯作者：
Wang, Yue
中科院分区：
文献类型：
--
作者：
Li, Zhiyuan;Pan, Wei;Wang, Yue
光动力疗法（PDT），一种新兴的方法，涉及光敏剂，光和分子氧，已显示出对抗牙周炎的前景。然而，PDT并不总是获得理想的治疗效果，因为一些光敏剂具有很强的疏水性，难以被牙周致病菌有效吸收。在这里，疏水性光敏剂二氢卟酚e6（Ce 6）通过与达特肽（一种阳离子细胞穿透肽）缀合而被修饰，以通过促进其与带负电荷的细胞壁的相互作用和穿透细胞膜来改善其溶解度并增强其细菌吸附。将所获得的TAT-Ce 6缀合物（TAT-Ce 6）用于制备负载临床上使用的抗生素药物替硝唑（TDZ）的自组装纳米颗粒（NPs），从而希望通过结合PDT和抗生素治疗来实现协同抗牙周炎作用。与游离Ce 6相比，TAT-Ce 6纳米粒对牙周病原菌的吸附和渗透能力显著增强，对牙周病原菌和单核巨噬细胞的PDT效率也显著提高。在635 nm激光照射下，载TDZ的TAT-Ce 6（TAT-Ce 6/TDZ）纳米粒在PDT和抗生素治疗中表现出显著的协同抗牙周炎作用，反映在体外对牙周致病菌的有效杀灭和在Sprague-Dawley大鼠牙周炎模型中牙槽骨的吸附减少。总之，本研究开发了一种新的光敏剂，可以有效地被牙周致病菌吸收，也提供了一个有效的联合策略PDT与抗生素治疗牙周炎的临床治疗。
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.