CAREER: Multiscale Modeling of Nanoparticle-Cell Interactions

在医学实践中，长期以来一直希望实现药物选择性递送至特定恶性细胞以使治疗功效最大化并使不良副作用最小化。 传统的药物输送系统在这方面并不成功，因为它们将药物均匀地分配到全身，不仅杀死靶细胞，还杀死健康细胞。 由于它们的小尺寸，配体涂覆的纳米颗粒（例如碳纳米管、量子点、树枝状聚合物等）可以通过配体-受体相互作用和识别有效地导向特定的细胞类型，从而为细胞水平的位点特异性药物递送开辟新的途径。该教师早期职业发展（CAREER）项目旨在通过一种新颖的多尺度模型来探索分子水平上的纳米颗粒-细胞相互作用机制，该模型将原子模拟，介观尺度粒子动力学，连续介质力学和化学动力学联系起来。纳米颗粒的表面和物理性质（粒度、形状、拓扑结构、配体-受体结合亲和力等）之间的关键相互关系并建立它们的细胞摄取速率和内吞途径。 参数研究将确定优化的参数，作为合理设计纳米药物载体的输入。成功完成拟议的研究将为实现基于纳米颗粒的定点给药系统铺平道路。从拟议的研究中开发的计算工具将随后帮助研究界解决纳米生物界面的其他根本性重要问题，这些问题无法单独通过实验进行系统和定量探索。该项目将提供一个多层次的平台，通过研究生、本科生和高中生的直接参与，培养下一代纳米生物技术科学家和工程师。这个令人兴奋的研究领域的亮点将被纳入将提供给大学和高中学生的专题讲座。

In medical practice, there has long been the desire to achieve selective delivery of drugs to specific malignant cells to maximize therapeutic efficacy and minimize adverse side effects. Traditional drug delivery systems have not been successful in this aspect because they uniformly distribute drugs to the whole body, killing not only the target cells but also the healthy ones. Owing to their small size, ligand-coated nanoparticles (such as carbon nanotubes, quantum dots, dendrimers, etc.) can be efficiently directed to a specific cell type through ligand-receptor interaction and recognition, thus opening new pathways for site-specific drug delivery at the cellular level. This Faculty Early Career Development (CAREER) project aims to probe the nanoparticle-cell interaction mechanisms at the molecular level through a novel multiscale model that links atomistic simulations, meso-scale particle dynamics, continuum mechanics, and chemical kinetics. Critical interrelationships between surface and physical properties of the nanoparticles (particle size, shape, topology, ligand-receptor binding affinity, etc.) and their cellular uptake rate and endocytic pathways will be established. Parametric studies will identify the optimized parameters, which serve as inputs for rational designs of nanoparticle-based drug carriers.Successful completion of the proposed research will pave the way towards the realization of nanoparticle-based site-specific drug delivery systems. The computational tools developed from the proposed research will subsequently aide the research community in addressing other fundamentally important issues at nano-bio interfaces that cannot be explored systematically and quantitatively by experiments alone. The project will provide a multi-level platform for training the next generation of scientists and engineers in nano-bio-technology through direct participation of graduate, undergraduate, and high-school students. Highlights from this exciting research area will be incorporated into special topics lectures that will be offered to both college and high-school students.