EAGER: Kinetic and biophysical approach to engineering targeted nanoparticles

EAGER：工程靶向纳米颗粒的动力学和生物物理方法

• 批准号: 1539114
• 负责人: Jered Haun
• 金额: $ 10万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1539114&HistoricalAwards=false
• 关键词: EAGER; Kinetic; biophysical; approach; engineering

1539114(Haun)The purpose of this research project is to develop targeted strategies for the delivery of therapies. The research involves exploration at the interface of binding targets such that the adhesion of targeted therapies is effectually enabled. The research will provide immense benefit through the development and advancement of strategies for treating disease without impairment to healthy cells, tissues and organs. In addition, this research will result in the decrease in the amount of drug therapies required as specificity and targeting is increased. This research will also propel the science of adhesion forward through the understanding of binding properties for surfaces. Improving capabilities to target diseases would change the way the diseases are detected and treated. It would enable early detection and personalized medicine capabilities, as well as lower adverse side-effects.This research project seeks to explore the development of nanomaterials as carriers for targeted delivery platforms. Developed nanomaterials will have high-loading capacities, will enable facile attachment of targeting moieties, and will have favorable pharmacokinetics. The research will involve the development of multo0valent nanoparticles. Adhesion dynamics will be controlled in these nanoparticle delivery systems. The goal for this work is to achieve the first experimental demonstration of superselectivity. The hypothesis is that precisely tuning kinetic and biophysical properties of the molecular binding interactions so that they are highly dynamic will result in exquisite sensitivity to bond valency. In this manner, adhesion to normal cells would only be transient in nature, but firm binding would occur at higher target levels or after de novo expression of a co-target. The hypothesis will be tested using vascular inflammation as a model via the target ICAM-1. The PI postulates that the transient binding paradigm proposed would enable a unique and exciting capability: active surveillance of the vascular wall for sites of disease.

1539114(豪恩)这项研究项目的目的是为提供治疗制定有针对性的战略。这项研究涉及探索结合靶点的界面，以便有效地实现靶向治疗的粘连。这项研究将通过开发和推进不损害健康细胞、组织和器官的治疗疾病的策略来提供巨大的好处。此外，随着特异性和靶向性的提高，这项研究将导致所需药物治疗量的减少。这项研究还将通过对表面结合特性的了解来推动附着力科学的发展。提高针对疾病的能力将改变检测和治疗疾病的方式。它将使早期发现和个性化药物治疗能力，以及较低的不良反应。本研究项目旨在探索发展纳米材料作为靶向给药平台的载体。开发的纳米材料将具有高负载能力，将使靶向部分容易附着，并将具有良好的药代动力学。这项研究将涉及多价纳米粒子的开发。在这些纳米颗粒输送系统中，附着动力学将受到控制。这项工作的目标是实现超选择性的第一个实验演示。这个假设是，精确地调整分子结合相互作用的动力学和生物物理性质，使它们具有高度的动力学性质，将导致对键价的精细敏感性。通过这种方式，与正常细胞的黏附本质上只是短暂的，但在较高的靶标水平上或在共靶标从头表达之后，将发生牢固的结合。这一假说将通过靶向ICAM-1以血管炎症为模型进行验证。PI假设，所提出的瞬时结合范例将实现一种独特而令人兴奋的能力：主动监测血管壁的疾病部位。