Mechanism of toxicity of aluminium-based adjuvant (ABA) nanomaterials

铝基佐剂（ABA）纳米材料的毒性机制

• 批准号: MR/J006939/1
• 负责人: Christopher Exley
• 金额: $ 41.41万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ006939%2F1
• 关键词: Mechanism; toxicity; aluminium; based; adjuvant

There is a burgeoning interest in human exposure to what have been called nanoparticulates. It has becomeapparent that sub-micron sized particles are able to enter the body and potentially accumulate in tissues andorgans. These nanomaterials are both novel materials which are being developed for myriad purposes andthey are materials which are 'naturally' present in many different environments as the products of bothnatural and man-made phenomena. While there is evidence that such nanomaterials are becoming morewidespread it is also clear that we understand very little about their potential modes of toxicity. Actually onesuch form of nanomaterial has been used by humans for decades and are the aluminium-based adjuvantswhich are used in approximately 80% of all human vaccinations. While these materials are highly biologicallyreactive we still do not understand fully how they work and we believe that they would be an extremelyuseful model system for understanding the toxicity of nanomaterials. The objectives of our research are toobtain a thorough understanding of the physical and chemical properties of these nanomaterials and theninvestigate how these influence their biological reactivity. We hope to explain how they work as adjuvantsand in doing so we will help in the design of future safe and effective adjuvant materials. In addition we arehoping to optimise the toxicity of such materials such that they might be used to kill tumour cells in cases ofmalignant brain cancer. None of these objectives can be achieved without an understanding of themechanisms of toxic action of these nanomaterials and this is the primary objective of this research.

人们对人类接触纳米颗粒的兴趣日益浓厚。很明显，亚微米大小的颗粒能够进入人体并可能在组织和器官中积聚。这些纳米材料都是为多种目的而开发的新型材料，并且它们是作为自然和人造现象的产物“自然”存在于许多不同环境中的材料。虽然有证据表明此类纳米材料正变得越来越广泛，但很明显，我们对其潜在毒性模式知之甚少。事实上，这种形式的纳米材料已经被人类使用了数十年，并且是铝基佐剂，约 80% 的人类疫苗接种都使用这种佐剂。虽然这些材料具有高度生物反应性，但我们仍然不完全了解它们的工作原理，但我们相信它们将成为了解纳米材料毒性的极其有用的模型系统。我们研究的目的是全面了解这些纳米材料的物理和化学性质，然后研究它们如何影响其生物反应性。我们希望解释它们如何作为佐剂发挥作用，这样我们将有助于设计未来安全有效的佐剂材料。此外，我们希望优化此类材料的毒性，以便它们可用于杀死恶性脑癌中的肿瘤细胞。如果不了解这些纳米材料的毒性作用机制，这些目标都无法实现，这是本研究的主要目标。

项目成果

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

深入了解临床批准的人类疫苗接种中使用的铝佐剂的细胞命运和毒性。

• DOI: http://dx.10.1038/srep31578
• 发表时间: 2016
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Mold M

Intracellular tracing of amyloid vaccines through direct fluorescent labelling.

通过直接荧光标记对淀粉样蛋白疫苗进行细胞内追踪。

• DOI: http://dx.10.1038/s41598-018-20845-9
• 发表时间: 2018
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Mold M

Unequivocal imaging of aluminium in human cells and tissues by an improved method using morin.

通过使用桑色素的改进方法对人体细胞和组织中的铝进行明确成像。

• DOI: http://dx.10.1007/s00418-019-01809-0
• 发表时间: 2019
• 期刊: Histochemistry and cell biology
• 影响因子: 2.3
• 作者: Mold MJ

Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

铝佐剂及其对吞噬细胞线粒体和溶酶体的影响。

• DOI: 10.1016/j.jinorgbio.2013.08.003
• 发表时间: 2013-11-01
• 期刊: Journal of inorganic biochemistry
• 影响因子: 3.9
• 作者: L. Ohlsson;C. Exley;A. Darabi;Emma S;én;én;P. Siesjö;H. Eriksson
• 通讯作者: H. Eriksson

Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line.

单核 THP-1 细胞系中胞内铝佐剂的明确鉴定。

• DOI: http://dx.10.1038/srep06287
• 发表时间: 2014
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Mold M