EAGER: Kinetic and biophysical approach to engineering targeted nanoparticles

1539114（Haun）这个研究项目的目的是制定有针对性的治疗策略。该研究涉及探索结合靶点的界面，从而有效地实现靶向治疗的粘附。这项研究将通过发展和推进治疗疾病而不损害健康细胞、组织和器官的策略，提供巨大的好处。此外，随着特异性和靶向性的增加，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理解推动粘附科学的发展。提高针对疾病的能力将改变发现和治疗疾病的方式。它将使早期检测和个性化医疗能力成为可能，并降低不良副作用。该研究项目旨在探索纳米材料作为靶向递送平台载体的发展。开发的纳米材料将具有高负载能力，将使靶向部分易于附着，并将具有良好的药代动力学。这项研究将涉及多价纳米颗粒的开发。在这些纳米颗粒输送系统中，粘附动力学将得到控制。这项工作的目标是实现超选择性的第一次实验演示。假设是，精确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态性，将导致对键价的高度敏感性。通过这种方式，与正常细胞的粘附在本质上只是短暂的，但在更高的靶标水平或重新表达共同靶标后，会发生牢固的结合。这一假设将通过靶ICAM-1以血管炎症为模型进行验证。PI假设提出的瞬时结合模式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。

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.