Predicting the Toxicity of Nanomaterials by a Transforming Protein Corona

通过转化蛋白电晕预测纳米材料的毒性

基本信息

批准号：
8625112
负责人：
Apparao Rao
金额：
$ 44.48万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-04 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8625112
关键词：
Address Adsorption Albumins Amino Acids Apolipoproteins Applications Grants Area Biochemical Biological Biological Availability Biophysics Blood Circulation Cells Cellular biology Charge Chemicals Citrates Competitive Binding Complement Computer Simulation Cosmetics Crowding Cytoskeletal Proteins Data Development Disease Endothelial Cells Engineering Environment Evolution Exhibits Food Funding Mechanisms Funding Opportunities Future G Actin Generations Goals Hardness Health Heavy Metals Human Hypersensitivity Image Immune response Immunoglobulin G In Vitro Injury Integral Membrane Protein Interdisciplinary Study Investigation Ions Knowledge Lipids Lung Mammalian Cell Measures Mechanics Mediating Medicine Membrane Mission Modeling Molecular Morphology Nanotechnology National Institute of Environmental Health Sciences Organism Oxides Peptides Phase Plasma Proteins Property Protein Dynamics Proteins Reaction Reproducibility Research Role Safety Science Scientist Secondary Protein Structure Silver Societies Spectrum Analysis Stress Structure Surface System Techniques Technology Testing Thermodynamics Time Tissues Toxic effect Toxicology Training Tubulin United States National Institutes of Health Universities Whole Organism aqueous extracellular graduate student in vivo knowledge base macrophage nanomaterials nanomedicine nanoparticle nanotoxicity nanotoxicology novel protein degradation protein structure public health relevance receptor response scavenger receptor stoichiometry undergraduate student uptake

项目摘要

Engineered nanomaterials have unique electrical, mechanical and physicochemical properties with potential to benefit our society. However, the health and safety of nanomaterials has recently become a great concern to the public, policymakers and regulatory agencies. Such concern is justified due to the vast potential use of nanomaterials in food, cosmetics, medicine, construction, manufacturing, and the environment. It has recently been established that nanomaterials, upon entry into the bloodstream or lung, exhibit a natural tendency of physical adsorption with proteins, peptides, lipids and amino acids to render a protein "corona" that may dictate the bioavailability and distribution of nanomaterials within the host system, at the cellular, tissue and organism level. Consequently, the objective of this application is to delineate the dynamic roles of nanoparticle-protein corona on biological responses to engineered nanomaterials for safe nanotechnologies and nanomedicines. Determining the health and safety implications of the nanoparticle-protein corona requires addressing the fundamental aspects of 1) dynamics and conformational changes resulting from competitive binding, crowding and degradation of the proteins, and 2) recognition of the protein corona by cellular receptors and immune responses. The central hypothesis of this project is that the physicochemical properties of the nanoparticle-protein corona entity are correlated with biological responses to the corona to impact on their uptake and hypersensitivity reactions. We will test this hypothesis by pursuing three specific aims: 1) Understand nanoparticle-protein interaction and transformation; 2) Determine the in silico structure and dynamics of protein corona; 3) Determine the in vitro impact of nanoparticle-protein corona on directing cellular uptake, ER stress and the unfolded protein response. The rationale of this application is that understanding the impact of nanoparticle-protein corona on cellular recognition, uptake and response is crucial for predicting toxicity and developing safe nanotechnologies. In addition, this R15 project is expected to contribute to the training of a new generation of scientists at the interface of biophysics and biomedicine and facilitate future NIH funding opportunities for Clemson University and East Carolina University.

工程纳米材料具有独特的电学、机械和物理化学性质有潜力造福我们的社会。然而，纳米材料的健康和安全问题最近成为公众、政策制定者和监管机构高度关注的问题。这样的由于纳米材料在食品、化妆品、医药、建筑、制造和环境。最近已经确定，纳米材料在进入血液或肺部后，表现出与蛋白质、肽、脂质和氨基酸物理吸附的自然倾向呈现出可能决定纳米材料的生物利用度和分布的蛋白质“冠状” 在宿主系统内，在细胞、组织和生物体水平上。因此，目标是该应用旨在描述纳米颗粒-蛋白质电晕对生物的动态作用对工程纳米材料的反应，以实现安全的纳米技术和纳米医学。确定纳米颗粒蛋白电晕对健康和安全的影响需要解决 1) 动力学和构象变化的基本方面蛋白质的竞争性结合、拥挤和降解，以及 2) 蛋白质的识别电晕通过细胞受体和免疫反应。该项目的中心假设是纳米颗粒-蛋白质冠实体的物理化学性质与对电晕的生物反应会影响其吸收和超敏反应。我们将通过追求三个具体目标来检验这一假设：1）了解纳米颗粒-蛋白质互动与转化； 2) 确定蛋白质的计算机结构和动力学电晕; 3) 确定纳米颗粒蛋白冠对细胞定向的体外影响摄取、内质网应激和未折叠蛋白反应。该申请的理由是了解纳米颗粒-蛋白质电晕对细胞识别、摄取和吸收的影响响应对于预测毒性和开发安全的纳米技术至关重要。此外，这 R15项目预计将有助于培养新一代科学家生物物理学和生物医学的接口，并促进未来 NIH 的资助机会克莱姆森大学和东卡罗来纳大学。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biomolecular Interactions and Biological Responses of Emerging Two-Dimensional Materials and Aromatic Amino Acid Complexes.

新兴二维材料和芳香氨基酸复合物的生物分子相互作用和生物反应。

DOI：
10.1021/acsami.6b04571
发表时间：
2016-06-21
期刊：
ACS applied materials & interfaces
影响因子：
9.5
作者：
Sai Sunil Kumar Mallineni;J. Shannahan;Achyut J. Raghavendra;A. Rao;Jared M Brown;R. Podila
通讯作者：
R. Podila

Influence of carbon nanomaterial defects on the formation of protein corona.

碳纳米材料缺陷对蛋白质冠形成的影响。

DOI：
发表时间：
2015
期刊：
影响因子：
3.9
作者：
Sengupta B;Gregory WE;Zhu J;Dasetty S;Karakaya M;Brown JM;Rao AM;Barrows JK;Sarupria S;Podila R
通讯作者：
Podila R

Biocorona formation contributes to silver nanoparticle induced endoplasmic reticulum stress.

生物冠的形成有助于银纳米颗粒诱导的内质网应激。

DOI：
10.1016/j.ecoenv.2018.11.107
发表时间：
2019-04-01
期刊：
Ecotoxicology and environmental safety
影响因子：
6.8
作者：
I. Persaud;J. Shannahan;Achyut J. Raghavendra;Nasser B Alsaleh;R. Podila;Jared M Brown
通讯作者：
Jared M Brown

Brushed polyethylene glycol and phosphorylcholine for grafting nanoparticles against protein binding.

刷过聚乙二醇和磷酸胆碱，用于接枝纳米颗粒以防止蛋白质结合。

DOI：
10.1039/c6py01480a
发表时间：
2016-12-07
期刊：
Polymer chemistry
影响因子：
4.6
作者：
Wang B;Blin T;Käkinen A;Ge X;Pilkington EH;Quinn JF;Whittaker MR;Davis TP;Ke PC;Ding F
通讯作者：
Ding F

Charge-transfer interactions induce surface dependent conformational changes in apolipoprotein biocorona.

电荷转移相互作用诱导载脂蛋白生物冠中表面依赖性构象变化。