EAGER: Kinetic and biophysical approach to engineering targeted nanoparticles

1539114（Haun）本研究项目的目的是开发用于治疗的靶向策略。该研究涉及在结合靶点的界面处的探索，使得靶向治疗的粘附有效地实现。该研究将通过开发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益处。此外，这项研究将导致所需的药物治疗量减少，因为特异性和靶向增加。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检测和治疗疾病的方式。该研究项目旨在探索开发纳米材料作为靶向输送平台的载体。 开发的纳米材料将具有高负载能力，将使靶向部分易于连接，并将具有有利的药代动力学。这项研究将涉及多价纳米颗粒的开发。 粘附动力学将在这些纳米颗粒递送系统中得到控制。这项工作的目标是实现超选择性的第一个实验证明。 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，使它们具有高度动态性，将导致对键价的灵敏度。以这种方式，与正常细胞的粘附本质上仅是短暂的，但牢固的结合将在更高的靶水平或在共同靶的从头表达后发生。将通过靶ICAM-1使用血管炎症作为模型来检验该假设。PI假设所提出的瞬时结合范例将实现独特且令人兴奋的能力：主动监视血管壁的疾病部位。

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.