金属纳米酶在菌斑生物膜相关口腔疾病防治中的研究进展

Research progress on the application of metal nanoenzymes in the prevention and treatment of plaque biofilm-associated oral diseases

摘要

口腔菌斑生物膜作为多种细菌生存、代谢的基础，使口腔细菌难以被清除。随着抗生素滥用造成的耐药菌群出现，菌斑生物膜相关口腔疾病的防治难度进一步增加。尽管目前在研究生物膜形成、破坏有关机制方面取得了一定进展，但可用于临床的有效治疗方案仍较缺乏。金属纳米酶具有纳米粒子的物理特性及类似天然酶的催化活性。金属纳米酶的纳米级尺寸提供了更大的比表面积，在发挥类酶作用产生大量活性氧的同时促进活性氧快速扩散到活性催化位点，增强纳米酶的抗氧化特性；同时金属纳米酶易通过电化学还原法、溶剂热合成法、微波辅助合成法等方法制取，且具有产生高浓度的羟基自由基、催化牙菌斑生物膜降解、氧化应激裂解葡聚糖抑制生物膜形成、释放金属离子杀灭细菌的潜力，有望成为防治口腔菌斑生物膜相关口腔疾病的新选择。金属纳米酶可通过口服、静脉注射、呼吸等方式进入生物体，但可能引发肺毒性、肝脏毒性、神经毒性等潜在毒性效应。在复杂的生物环境下，金属纳米酶毒性的发生可能涉及多重机制，其作用机制和安全性评价有待深入研究。本文拟从金属纳米酶的特性、抗菌机制、生物毒性及其在菌斑生物膜相关口腔疾病防治中的应用等多个方面阐述金属纳米酶的研究进展，为口腔疾病的防治提供新思路。

Abstract

Oral plaque biofilms are one of the bases for the survival and metabolism of different bacteria. With the emergence of drug-resistant bacteria due to antibiotic abuse, the prevention and treatment of plaque biofilm-associated oral diseases are becoming increasingly difficult. Although some research progress has been made in the field of biofilm formation and destruction, there is still a lack of effective clinical therapies for plaque biofilm-associated oral diseases. Metal nanoenzymes possess the physical properties of nanoparticles and exhibit catalytic activity similar to that of natural enzymes. The nanoscale size of metal nanoenzymes provides a greater specific surface area to help reactive oxygen species spread rapidly to active catalytic sites and improve the antioxidant properties of nanoenzymes. Additionally, metal nanoenzymes are easy to produce using different methods, such as electrochemical reduction, solvent thermal synthesis and microwave-assisted synthesis. Moreover, metal nanoenzymes can produce a high concentration of hydroxyl radicals, catalyze plaque biofilm degradation, lyse glucan and inhibit biofilm formation by oxidative stress reactions, as well as kill bacteria by releasing metal ions. Thus, metal nanoenzymes are expected to become a new option for the prevention and treatment of oral plaque biofilm-associated diseases. However, metal nanoenzymes can enter organisms through oral, intravenous and respiratory routes, triggering potential toxic effects such as pulmonary toxicity, hepatotoxicity and neurotoxicity. In a complex biological environment, the occurrence of metal nanoenzymes toxicity may involve multiple mechanisms, and the mechanism of action and safety need to be thoroughly investigated. In this paper, we intend to describe the research progress on metal nanoenzymes through an overview of their properties, antibacterial mechanisms, biotoxicity and applications in the prevention and treatment of oral plaque biofilm-related diseases, which may provide new ideas for the prevention and treatment of these diseases.

关键词

金属纳米酶 / 纳米酶 / 人工酶 / 人工纳米材料 / 纳米粒子 / 活性氧 / 氧化应激 / 菌斑生物膜 / 生物膜 / 口腔疾病 / 生物毒性

Key words

metal nanoenzymes / nanoenzymes / artificial enzymes / artificial nanomaterials / nanoparticles / reactive oxygen species / oxidative stress / plaque biofilm / biofilm / oral disease / biological toxicity

Author summay

李昊，医学博士，教授，博士生导师。于四川大学华西口腔医学院获博士学位，美国哈佛大学附属福赛斯研究院访问学者，现任广西口腔颌面修复与重建研究重点实验室副主任、广西医科大学口腔医学院/附属口腔医院口腔修复科副主任、广西口腔医学会口腔修复学专业委员会副主任委员、中华口腔医学会口腔修复学专业委员会委员、中华口腔医学会口腔材料学专业委员会委员等。主要研究方向为口腔颌面部骨缺损修复与骨免疫。主持研究课题10余项，包括国家自然科学基金项目2项、广西自然科学基金项目3项等。已在国内外专业期刊上发表学术论文70余篇，参编专著2本，获得国内发明专利1项、实用新型专利1项，获得广西科技进步奖三等奖1项、广西医药卫生适宜技术推广奖一等奖1项。担任J Cell Mol Med、Drug Des Devel Ther、J Periodontol、AAPS Pharm Sci Tech、Immun Inflamm Dis等国际SCI期刊审稿人。