摘要
由细菌生物膜造成的耐药是感染性疾病的临床挑战,严重危害人类健康.细菌定植在机体后产生胞外基质形成生物膜,其具有结构致密、高黏附性、药物低渗等特征,是临床传统药物治疗感染性疾病失败的关键原因.因此,亟待开发抗细菌生物膜感染的新型治疗策略,应对日益严峻的耐药感染.纳米生物材料具有特异靶向、智能递送、载药量高、毒副性低、穿透性强等优势,被广泛用于细菌生物膜相关感染的治疗.本文阐述了细菌生物膜的生物学特性及其耐药分子机制,介绍了纳米生物材料通过破坏成熟生物膜、阻断细菌通信、抑制细菌代谢和增强生物膜渗透等策略治疗细菌感染的进展,并展望了纳米材料生物治疗的发展趋势与转化前景.
Abstract
Bacterial biofilms gave rise to persistent infections and multi-organ failure,thereby posing a serious threat to human health.Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances(EPS),such as proteins,polysaccharides,and eDNA,which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces.They had the characteristics of dense structure,high adhesiveness and low drug permeability,and had been found in many human organs or tissues,such as the brain,heart,liver,spleen,lungs,kidneys,gastrointestinal tract,and skeleton.By releasing pro-inflammatory bacterial metabolites including endotoxins,exotoxins and interleukin,biofilms stimulated the body's immune system to secrete inflammatory factors.These factors triggered local inflammation and chronic infections.Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections,it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections.Based on the nanoscale structure and biocompatible activity,nanobiomaterials had the advantages of specific targeting,intelligent delivery,high drug loading and low toxicity,which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms.This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials.For example,nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms,and effectively increased the drug enrichment within biofilms.By loading quorum sensing inhibitors,nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms.Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients.Moreover,energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication.Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods,ultrasound,and magnetic field,and deliver drugs to the infection sites accurately.Achieving this using conventional drugs was difficult.Overall,the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms,and highlighted therapeutic strategies from different perspectives by nanobiomaterials,such as dispersing bacterial mature biofilms,blocking quorum sensing,inhibiting bacterial metabolism,and energy driving penetration.In addition,we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections.Firstly,the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity,which created exacting requirements for the design,construction and preparation process of nanobiomaterials.Secondly,biofilm disruption carried the risk of spread and infection the pathogenic bacteria,which might lead to other infections.Finally,we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
基金项目
国家重点研发计划(2023YFA0915600)
国家自然科学基金(82372271)
深圳市 科技计 划(JCYJ20210324115611032)
深圳市 科技计 划(JCYJ20220530163005012)
深圳市 科技计 划(JSGG20220606141001003)
深圳市 科技计 划(JCYJ20210324132012035)
深圳市结核病临床医学研究中心(20210617141509001)
深圳市高水平医院建设专项经费(23250G1005)
深圳市高水平医院建设专项经费(22240G1001)
深圳市高水平医院建设专项经费(24250G1027)
深圳市高水平医院建设专项经费(24250G1019)
NETL
NSTL
万方数据