ZnO-loaded DNA nanogels as neutrophil extracellular trap-like structures in the treatment of mouse peritonitis

IF 8.1 1区 工程技术 Q1 MATERIALS SCIENCE, BIOMATERIALS Materials science & engineering. C, Materials for biological applications Pub Date : 2021-12-01 DOI:10.1016/j.msec.2021.112484
Yu-Fon Chen , Yee-Hsuan Chiou , Yi-Cheng Chen , Yi-Sheng Jiang , Ting-Yuan Lee , Jeng-Shiung Jan
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引用次数: 5

Abstract

Neutrophil extracellular traps (NETs) are chromatin-based structures that are released from neutrophils during infections and prevent microbes from spreading in the body through efficient degradation of their composition. Based on this chromatin-driven strategy of capturing and killing bacteria, we designed NET-like structures using DNA and ZnO nanoparticles (NPs). DNA was first purified from kiwifruit and treated with HCl to increase hydroxyl groups in the opened-deoxylribose form. The carboxyl groups of citric acid were then thermally crosslinked with said hydroxyl and primary amine groups in DNA, forming DNA-HCl nanogels (NGs). ZnO NPs were then used as positively charged granule enzymes, adsorbed onto the DNA-HCl NG, obtaining ZnO/DNA-HCl NGs (with NET biomimicry). In an anti-inflammatory assay, ZnO/DNA-HCl NGs significantly inhibited TNF-α, IL-6, iNOS and COX-2 expression in LPS-stimulated Raw264.7 cells. Moreover, the ZnO/DNA-HCl NGs markedly alleviated clinical symptoms in LPS-induced mouse peritonitis. Finally, ZnO/DNA-HCl NGs suppressed E. coli from entering circulation in septic mice while prolonging their survival. Our results suggest that the ZnO/DNA-HCl NGs, which mimic NET-like structures in the blocking of bacteria-inducted inflammation, may be a potential therapeutic strategy for bacterial infections.

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负载zno的DNA纳米凝胶作为中性粒细胞胞外陷阱样结构治疗小鼠腹膜炎
中性粒细胞胞外陷阱(NETs)是一种基于染色质的结构,在感染期间由中性粒细胞释放,并通过有效降解其成分来防止微生物在体内扩散。基于这种染色质驱动的捕获和杀死细菌的策略,我们使用DNA和ZnO纳米颗粒(NPs)设计了net样结构。首先从猕猴桃中纯化DNA,并用盐酸处理以增加开放脱氧核糖形式的羟基。然后,柠檬酸的羧基与DNA中的羟基和伯胺基团热交联,形成DNA- hcl纳米凝胶(ng)。然后将ZnO NPs作为带正电的颗粒酶,吸附在DNA-HCl NG上,得到ZnO/DNA-HCl NGs(具有NET仿生)。在抗炎实验中,ZnO/DNA-HCl ng显著抑制lps刺激的Raw264.7细胞中TNF-α、IL-6、iNOS和COX-2的表达。此外,ZnO/DNA-HCl NGs可显著缓解lps诱导的小鼠腹膜炎的临床症状。最后,ZnO/DNA-HCl NGs抑制大肠杆菌进入脓毒症小鼠的循环,延长其存活时间。我们的研究结果表明,ZnO/DNA-HCl NGs可以模拟net样结构来阻断细菌诱导的炎症,可能是一种潜在的治疗细菌感染的策略。
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来源期刊
CiteScore
12.60
自引率
0.00%
发文量
28
审稿时长
3.3 months
期刊介绍: Materials Today is a community committed to fostering the creation and sharing of knowledge and experience in materials science. With the support of Elsevier, this community publishes high-impact peer-reviewed journals, organizes academic conferences, and conducts educational webinars, among other initiatives. It serves as a hub for advancing materials science and facilitating collaboration within the scientific community.
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