Selectively Antibacterial Silver-Gold Alloy Nanoparticles Conjugated with Target Specific Aptamer Sequences
与目标特异性适体序列缀合的选择性抗菌银金合金纳米粒子
基本信息
- 批准号:356685838
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2018
- 资助国家:德国
- 起止时间:2017-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Implant- associated infections occur in many different medical disciplines and are one of the most important challenges in modern medicine. These infections are caused by bacteria organised in complex biofilms which are highly resistant to antibiotics and to the host's immune system. This can often lead to loss of the implant and - in some disciplines - even to life-threatening complications. Antibacterial implant surfaces and active substances have been used for prophylaxis or therapy. However, these have the disadvantage that bacterial cells cannot be selectively and effectively treated without causing long-term damage to human cells too. Consequently, there is great need for innovative anti-infective strategies with a broadened therapeutic window.In this project, targeting silver-gold alloy nanoparticles (AgAu-NP) with specific activity against selected pathogenic bacteria will be developed. This involves combining the properties of antibacterial but also cytotoxic Ag-NP and highly biocompatible Au-NP. Here silver is responsible for the bactericidal activity by Ag+ ion release, whereas gold is meant to increase particle stability, to control ion release and to allow conjugation with target-specific aptamers via gold-thiol chemistry. To this end stable AgAu-NPs are synthesised by using an advanced laser-based method, which allows synthesis of these alloy nanoparticles with controlled composition, while the resulting NPs are conjugated ex situ with thiolated aptamer sequences. In this context the influence of particle composition (AgAu) and particle size on metal ion release, surface coverage and conjugation efficiency during bioconjugation as well as the formation of soluble and insoluble silver species in different media will be systematically examined. Due to specific binding of these AgAu-NP-conjugates to the bacterial membrane of relevant bacteria like S. aureus and P. gingivalis the pathogens are exposed to a high local Ag+ concentrations found in the vicinity of the particles which selectively inhibits the growth of this bacterium, even in the presence of other strains. In order to deduce the ideal NP composition and to achieve maximal antibacterial activity combined with minimal toxicity, a variety of systematic molecular biological assays and cell culture tests will be performed. This includes co-culture models of different bacteria strains as well as of relevant bacteria parallel to human cells. Selective binding experiments will explore the possibility of a specific association of the AgAu-NP-conjugates to the bacteria, while, furthermore, cellular uptake is examined in order to elucidate the mechanism of bactericidal activity. The planned experiments provide a highly innovative procedure for the treatment of bacterial infections and will elucidate basic scientific knowledge on how bioconjugation is affected by NP composition.
植入体相关感染发生在许多不同的医学学科中,是现代医学中最重要的挑战之一。这些感染是由组织在复杂生物膜中的细菌引起的,这些细菌对抗生素和宿主的免疫系统具有高度耐药性。这通常会导致植入物的丢失,在某些学科中甚至会导致危及生命的并发症。抗菌种植体表面和活性物质已用于预防或治疗。然而,这些方法有一个缺点,即细菌细胞不能被选择性和有效地治疗,而不会对人类细胞造成长期损害。因此,非常需要具有拓宽治疗窗口的创新抗感染策略。本项目将开发针对特定致病菌具有特异性活性的靶向银金合金纳米颗粒(AgAu-NP)。这包括结合抗菌和细胞毒性Ag-NP和高度生物相容性Au-NP的特性。在这里,银通过银离子释放负责杀菌活性,而金的目的是增加颗粒稳定性,控制离子释放,并通过金-硫醇化学与目标特异性适配体结合。为此,稳定的AgAu-NPs通过一种先进的基于激光的方法合成,这种方法可以控制这些合金纳米颗粒的组成,而所得的NPs则与巯基适配体序列进行非原位共轭。在此背景下,颗粒组成(AgAu)和颗粒大小对金属离子释放、表面覆盖和生物偶联效率的影响,以及在不同介质中形成可溶性和不溶性银的影响将被系统地研究。由于这些agau - np偶联物与相关细菌(如金黄色葡萄球菌和牙龈卟啉卟啉菌)的细菌膜的特异性结合,病原体暴露于颗粒附近的高浓度局部Ag+,这选择性地抑制了这种细菌的生长,即使在其他菌株存在的情况下也是如此。为了推断出理想的NP组成并实现最大的抗菌活性和最小的毒性,将进行各种系统的分子生物学测定和细胞培养试验。这包括不同细菌菌株的共培养模型以及与人类细胞平行的相关细菌。选择性结合实验将探索agau - np偶联物与细菌特异性结合的可能性,同时,进一步研究细胞摄取以阐明杀菌活性的机制。计划中的实验为细菌感染的治疗提供了一个高度创新的过程,并将阐明关于NP组成如何影响生物偶联的基本科学知识。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Professor Dr.-Ing. Stephan Barcikowski其他文献
Professor Dr.-Ing. Stephan Barcikowski的其他文献
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{{ truncateString('Professor Dr.-Ing. Stephan Barcikowski', 18)}}的其他基金
Process-adaption of silver dispersions to laser-based manufacture of conductive paths in organic varnishes
银分散体的工艺适应于基于激光的有机清漆中导电路径的制造
- 批准号:
280970708 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Research Grants
Advanced X-Ray Imaging Study on the Mechanism of Nanoparticle Formation during Laser Ablation in Liquid
液体激光烧蚀过程中纳米颗粒形成机制的先进 X 射线成像研究
- 批准号:
262558940 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Research Grants
Impedance optimization by electrophoretic deposition of laser-generated colloidal nanoparticles on the surface of platinum-iridium macroelectrodes for deep brain stimulation and platinum-tungsten microelectrodes for recording of neural activity
通过在用于深部脑刺激的铂-铱大电极和用于记录神经活动的铂-钨微电极表面上电泳沉积激光产生的胶体纳米颗粒来优化阻抗
- 批准号:
201925000 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Vitalitätserhaltende Markierung von Spermien mit einer Y-chromosomenspezifischen Gensequenz durch lasergenerierte Goldnanopartikel-Biokonjugate
使用激光生成的金纳米颗粒生物共轭物对精子进行 Y 染色体特异性基因序列的活力保存标记
- 批准号:
213561943 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Influence of metal and alloy nanoparticles on germ cell function and embryo development - REPROTOX -
金属和合金纳米颗粒对生殖细胞功能和胚胎发育的影响 - REPROTOX -
- 批准号:
192487250 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Priority Programmes
In-Situ-Konjugation von Nanopartikeln beim Ultrakurzpuls-Laserstrahlabtragen in Monomerlösungen für das Elektrospinnen auf Brandwunden
超短脉冲激光束烧蚀单体溶液中纳米粒子的原位共轭,用于烧伤创面静电纺丝
- 批准号:
79172988 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Priority Programmes
NSF-DFG: Nonequilibrium thermal processing of nanoparticles: Laser melting and fragmentation in liquid
NSF-DFG:纳米粒子的非平衡热处理:液体中的激光熔化和破碎
- 批准号:
521278458 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
Dispersion effects of nanocomposites to improve melting and resolidification behavior during PBF-LB/P with near-infrared diode lasers
纳米复合材料的色散效应可改善近红外二极管激光器 PBF-LB/P 过程中的熔化和再凝固行为
- 批准号:
409779181 - 财政年份:
- 资助金额:
-- - 项目类别:
Priority Programmes
The transition between plasmon resonance and photoluminescence in coinage metal and alloy nanoclusters (NC) is controlled by surface charge, core composition, and surface ligand type
造币金属和合金纳米团簇 (NC) 中等离子共振和光致发光之间的转变由表面电荷、核心组成和表面配体类型控制
- 批准号:
320907882 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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Basic study of antibacterial biliary stent with silver containing and MPC polymer coating
含银MPC聚合物涂层抗菌胆道支架的基础研究
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