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Mechano-targeting of nanoparticles to atherogenic endothelium

纳米粒子机械靶向致动脉粥样硬化内皮

基本信息

批准号：
8919446
负责人：
PETER J BUTLER
金额：
$ 17.29万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
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：
2014-09-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8919446
关键词：
Adhesions Antibodies Area Atherosclerosis Binding Biochemical Blood flow Cell Line Cell Surface Receptors Cell membrane Cell surface Cells Characteristics Complement Data Dependence Detection Development Disease Drug Delivery Systems Dyes Effectiveness Endocytosis Endothelial Cells Endothelium Environment Experimental Designs Fluorescence Foundations Future Goals Health In Situ Knowledge Lead Ligands Liquid substance Malignant Bone Neoplasm Malignant Neoplasms Measurement Measures Mechanics Mediator of activation protein Membrane Methodology Methods Modeling Particle Size Pathology Physiological Property Protocols documentation Research Surface Surface Properties Testing Thermodynamics Tissues Vascular Endothelium Work apical membrane atherogenesis atheroprotective base cell type design improved mathematical model nanocarrier nanoparticle novel particle receptor mediated endocytosis research study response shear stress theranostics uptake

项目摘要

DESCRIPTION (provided by applicant): The goal of the proposed work is to develop a method for the targeting of nanoparticles (NPs) to endothelial cells that capitalizes on the intrinsic changes in mechanics of the cell surface accompanying diseases such as atherosclerosis and cancer. The main strategy to accomplish this goal is to measure the mechanical properties of the cell surface and how these properties change with disease state, and to design NPs that are more likely to be taken up by cells. The project will be specifically relevant to atherosclerosis since all studies will be on endothelial cells, the cells that line blod vessels, and the ones that are the initial mediators of the development of atherosclerosis. The first aim is to determine the effects of fluid shear stress on the membrane bending modulus in endothelial cells because blood-flow-induced shear stress is strongly associated with atherosclerosis. The second aim is to determine the relationship between membrane bending and ideal NP size for uptake. This aim will provide the first measurements of bending moduli associated with disease and use this information to improve delivery of NPs to diseased tissues. The third aim is to develop a mathematical model that will assist in the design of experimental protocols and optimization of NP size for targeting of diseased cells. This research will provide the underlying relationship between cell surface mechanics and NP uptake. It will investigate this phenomenon in the context of atherosclerosis and lay a foundation for future studies on mechanobiology-related diseases such as cancer and bone degeneration.

描述（由申请人提供）：拟议工作的目标是开发一种将纳米颗粒（NP）靶向内皮细胞的方法，该方法利用伴随疾病（如动脉粥样硬化和癌症）的细胞表面力学的内在变化。实现这一目标的主要策略是测量细胞表面的机械特性以及这些特性如何随疾病状态而变化，并设计更有可能被细胞吸收的NP。该项目将特别与动脉粥样硬化有关，因为所有的研究都将针对内皮细胞，即血管内皮细胞，以及动脉粥样硬化发展的初始介质。第一个目的是确定流体剪切应力对内皮细胞膜弯曲模量的影响，因为血流诱导的剪切应力与动脉粥样硬化密切相关。第二个目的是确定膜弯曲和理想的NP尺寸之间的关系。这一目标将提供与疾病相关的弯曲模量的第一次测量，并使用此信息来改善NP向患病组织的递送。第三个目标是开发一个数学模型，这将有助于设计实验方案和优化NP大小，以靶向病变细胞。这项研究将提供细胞表面力学和NP摄取之间的潜在关系。这将在动脉粥样硬化的背景下研究这种现象，并为未来研究与机械生物学相关的疾病，如癌症和骨退化奠定基础。