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新型纳米技术和近红外光动力疗法杀死牙周炎相关生物膜病原体并保护牙周组织。

Novel nanotechnology and near-infrared photodynamic therapy to kill periodontitis-related biofilm pathogens and protect the periodontium.

机构信息

Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.

The Dental College of Georgia, Augusta University, Augusta, GA, USA.

出版信息

Dent Mater. 2019 Nov;35(11):1665-1681. doi: 10.1016/j.dental.2019.08.115. Epub 2019 Sep 21.

Abstract

OBJECTIVE

Periodontal tissue destruction and tooth loss are increasingly a worldwide problem as the population ages. Periodontitis is caused by bacterial infection and biofilm plaque buildup. Therefore, the objectives of this study were to: (1) develop a near-infrared light (NIR)-triggered core-shell nanostructure of upconversion nanoparticles and TiO (UCNPs@TiO), and (2) investigate its inhibitory effects via antibacterial photodynamic therapy (aPDT) against periodontitis-related pathogens.

METHODS

The core β-NaYF:Yb,Tm were synthesized via thermal decomposition and further modified with the TiO shell via a hydrothermal method. The core-shell structure and the upconversion fluorescence-induced aPDT treatment via 980nm laser were studied. Three periodontitis-related pathogens Streptococcus sanguinis (S. sanguinis), Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) were investigated. The killing activity against planktonic bacteria was detected by a time-kill assay. Single species 4-day biofilms on dentin were tested by live/dead staining, colony-forming units (CFU), and metabolic activity.

RESULTS

The hexagonal shaped UCNPs@TiO had an average diameter of 39.7nm. UCNPs@TiO nanoparticles had positively charged (+12.4mV) surface and were biocompatible and non-cytotoxic. Under the excitation of NIR light (980nm), the core NaYF:Yb,Tm UCNPs could emit intense ultraviolet (UV) light, which further triggered the aPDT function of the shell TiO via energy transfer, thereby realizing the remarkable antibacterial effects against planktons and biofilms of periodontitis-associated pathogens. NIR-triggered UCNPs@TiO achieved much greater reduction in biofilms than control (p<0.05). Biofilm CFU was reduced by 3-4 orders of magnitude via NIR-triggered aPDT, which is significantly greater than that of negative control and commercial aPDT control groups. The killing efficacy of UCNPs@TiO-based aPDT against the three species was ranked to be: S. sanguinis<F. nucleatum=P. gingivalis. Metabolic activities of biofilms were also greatly reduced via NIR-triggered aPDT (p<0.05).

SIGNIFICANCE

Upconversion fluorescence-based aPDT achieved strong inhibiting effects against all three species of periodontitis-related pathogens. This novel nanotechnology demonstrated a high promise to inhibit periodontitis, with exciting potential to combat other oral infectious diseases such as deep endodontic infections.

摘要

目的

随着人口老龄化,牙周组织破坏和牙齿缺失日益成为全球性问题。牙周炎是由细菌感染和生物膜菌斑积聚引起的。因此,本研究的目的是:(1)开发上转换纳米粒子和 TiO 的近红外光(NIR)触发的核壳纳米结构(UCNPs@TiO);(2)通过抗菌光动力疗法(aPDT)抑制牙周炎相关病原体。

方法

通过热分解合成核β-NaYF:Yb,Tm,然后通过水热法进一步用 TiO 壳修饰。研究了核壳结构和通过 980nm 激光诱导的上转换荧光 aPDT 治疗。研究了三种牙周炎相关病原体:血链球菌(S. sanguinis)、牙龈卟啉单胞菌(P. gingivalis)和具核梭杆菌(F. nucleatum)。通过时间杀灭试验检测对浮游细菌的杀灭活性。通过活/死染色、菌落形成单位(CFU)和代谢活性测试牙本质上 4 天单种生物膜。

结果

六方形状的 UCNPs@TiO 的平均直径为 39.7nm。UCNPs@TiO 纳米粒子具有正电荷(+12.4mV)表面,具有生物相容性且无细胞毒性。在近红外光(980nm)激发下,核 NaYF:Yb,Tm UCNPs 可以发射出强烈的紫外(UV)光,进一步通过能量转移触发壳 TiO 的 aPDT 功能,从而实现对牙周炎相关病原体浮游生物和生物膜的显著抗菌作用。与对照组相比,NIR 触发的 UCNPs@TiO 对生物膜的减少作用更大(p<0.05)。通过 NIR 触发的 aPDT,生物膜 CFU 减少了 3-4 个数量级,明显大于阴性对照和商业 aPDT 对照组。UCNPs@TiO 基 aPDT 对三种物种的杀菌效果排名为:S. sanguinis<F. nucleatum=P. gingivalis。通过 NIR 触发的 aPDT,生物膜的代谢活性也大大降低(p<0.05)。

意义

基于上转换荧光的 aPDT 对所有三种牙周炎相关病原体均具有很强的抑制作用。这种新型纳米技术有望抑制牙周炎,具有治疗其他口腔感染性疾病(如深部牙髓感染)的巨大潜力。

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