纳米银复合材料与抗生素的联合抗菌性能及相关机制研究
Combined Antibacterial Property and Mechanism of Nanosilver Composites and Antibiotics against Bacteria
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摘要: 抗生素的滥用导致细菌耐药问题日益严重，人类迫切需要开发出新的抗菌药物以减少细菌耐药问题。基于纳米银制备而成的纳米银复合材料在兼顾纳米银抗菌性能的同时不仅能够克服单一纳米银释放速度快、不稳定等缺点，还能缓解细菌耐药的问题，因此被认为是一类具有广泛应用前景的新型抗菌剂。已有研究表明，单一纳米银与某些抗生素的联合使用可以达到协同抗菌效果，但目前尚缺乏对纳米银复合材料与抗生素的联合抗菌性能及机制的研究。本文首先制备出3种不同结构的纳米银复合材料，包括二氧化硅-聚多巴胺-纳米银复合材料(SiO2-PD-AgNPs)、纳米银@二氧化硅复合材料(AgNPs@SiO2)和纳米银@二氧化硅-聚多巴胺-纳米银复合材料(AgNPs@SiO2-PD-AgNPs)。随后测定了纳米银复合材料对大肠杆菌(Escherichia coli, E. coli)和枯草芽孢杆菌(Bacillus subtilis, B. subtilis)的单一毒性效应。结果显示，AgNPs@SiO2-PD-AgNPs复合材料对2种菌的单一毒性均大于其余2种纳米银复合材料。因此，笔者以AgNPs@SiO2-PD-AgNPs作为代表，测定了纳米银复合材料与硫酸卡那霉素(kanamycin sulfate, KS)/盐酸土霉素(oxytetracycline hydro-chloride, OH)的二元联合抗菌性能，发现AgNPs@SiO2-PD-AgNPs与KS联合可以对E. coli产生协同效应。协同效应产生的主要原因可能是：AgNPs@SiO2-PD-AgNPs释放出的纳米银会和KS发生键合反应生成KS-纳米银复合物，导致纳米银释放出大量的Ag+增加了细胞膜的通透性，从而使得进入细菌内的Ag+和KS比单独作用时进入胞内的抗菌剂增多，产生更强的抗菌性能，从而表现出协同抗菌效应。本研究基于新型纳米银复合材料与抗生素的联合抗菌性能实验探究了纳米银复合材料与特定抗生素联合用药的最佳组合和相关机制，为今后开发新型抗菌材料提供了新思路并为相关联合用药提供参考。Abstract: The abuse of antibiotics has caused increasingly serious problem of bacterial resistance, thus it is urgent to develop new antibacterial drugs to alleviate this problem. The nanosilver composites that was synthesized from single nanosilver can not only overcome the shortcomings of nanosilver, such as the rapid release rate of Ag+ and unstable physicochemical property, but also reduce the bacterial resistance, which are regarded as a new kind of antibacterial agents with broad application prospects. Previous studies have showed that the combination of single nanosilver and some antibiotics could exhibit the synergistic antibacterial effect. However, little information is available on the performance and mechanism of nanosilver composites combined with antibiotics. In this paper, three kinds of nanosilver composites with different structures were synthesized: silica-polydopamine-nanosilver (SiO2-PD-AgNPs), nanosilver@silica (AgNPs@SiO2) and nanosilver@silica-polydopamine-nanosilver (AgNPs@SiO2-PD-AgNPs). Subsequently, the single toxicity of nanosilver composites to Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) was determined. The results showed that the toxicity of AgNPs@SiO2-PD-AgNPs to the two kinds of bacteria were greater than that of the other two nanosilver composites. Therefore, AgNPs@SiO2-PD-AgNPs was selected as the representative to determine its combined antibacterial property with KS (kanamycin sulfate)/OH (oxytetracycline hydrochloride), and it was found that the combination of AgNPs@SiO2-PD-AgNPs and KS could display synergistic effect on E. coli/. The nanosilver released by AgNPs@SiO2-PD-AgNPs could react with KS to form the KS-nanosilver complex, resulting in a large amount of Ag+ released from nanosilver. The increase of Ag+ enhanced the permeability of cell membrane, so the amount of Ag+ and KS entering the bacteria were more than that of the antibacterial agents when acting alone, which resulted in greater antibacterial property and a synergistic effect. This study explores the optimal combination and related mechanism of new nanosilver composite and specific antibiotics based on the combined toxicity experiments, which will provide new insight into the development of new antibacterial materials and give a reference for the related combination application of drugs.
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