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Disease-Induced Modification in Nanoparticle-Corona Identity and Toxicity

疾病引起的纳米颗粒电晕特性和毒性的改变

基本信息

批准号：
9392983
负责人：
Jonathan Henry Shannahan
金额：
$ 24.9万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9392983
关键词：
Address Animal Model Area Atherosclerosis Biodistribution Biological Biology Blood Vessels Cardiovascular Diseases Cell Surface Receptors Cell surface Cells Characteristics Chronic Chronic Disease Complex Contrast Media Data Development Dextrans Disease Drug Delivery Systems Electron Microscopy Endothelial Cells Environment Evaluation Flow Cytometry Goals Health Human Hyperlipidemia In Vitro Individual Inductively Coupled Plasma Mass Spectrometry Inflammation Knowledge Lipids Magnetic Resonance Imaging Mediating Metabolic syndrome Microscopy Modification Obesity Pattern Physiological Population Production Property Proteins Proteomics Publications Reactive Oxygen Species Role Safety Serum Serum Proteins Silver Testing Therapeutic Time Toxic effect Toxicology Variant antimicrobial cell type cellular targeting clinically relevant cytotoxicity design in vivo inflammatory marker interdisciplinary approach interest iron oxide macromolecule macrophage metabolomics nanofabrication nanomaterials nanomedicine nanoparticle nanotherapeutic nanotoxicity nanotoxicology novel public health relevance receptor response screening surface coating uptake

项目摘要

DESCRIPTION (provided by applicant): Nanomaterials are increasingly being utilized for biomedical applications as therapeutics and drug delivery systems. Following their introduction into a physiological environment they rapidly associate a variety of macromolecules forming a corona. This corona modifies the size and interactive interface of the nanomaterial resulting in altered bio distribution, clearance, activity, and toxicity. The composition of the corona is dependent on the physicochemical properties of the nanomaterial, as well as, the physiological environment. To date most evaluation of nanomaterial toxicity is performed under normal, healthy conditions. However, due to the vast and growing portion of our population that suffer from chronic conditions such as obesity and cardiovascular diseases these nanomaterials will not be introduced into healthy physiological environments. In this proposal we hypothesize that an underlying condition known to alter serum protein and lipid content, hyperlipidemia, will modify the corona that forms on nanomaterials as will different sizes and therapeutic surface coatings. Further we will examine how these modifications in coronal composition influence cellular uptake, in vivo bio distribution, subcellular localization, intracellular fate, and toxiciy. To test this hypothesis we will utilize iron oxide nanoparticles, which are currently in development for biomedical applications including their use as MRI contrast agents and silver nanoparticles, which are being used for their antimicrobial/fungal properties. Cellular interactions and toxicological effects will be examined in macrophages and endothelial cells to represent two key cell types that will interact with nanomaterials and are critical in inflammation and vascular biology. Ultimately, through a thorough understanding of the corona and its biological consequences gained from this proposal, we can develop effective nanotherapeutics with limited toxicological implications.