CAREER: Multiscale Modeling of Nanoparticle-Cell Interactions

这个学院早期职业发展项目旨在通过一个新的多尺度模型在分子水平上探索纳米粒子与细胞的相互作用机制，该模型将原子模拟、介观粒子动力学、连续介质力学和化学动力学联系在一起。在医学实践中，长期以来，人们一直希望实现选择性地将药物输送到特定的恶性肿瘤细胞，以最大限度地提高治疗效果，并将副作用降至最低。传统的药物传递系统在这方面并不成功，因为它们将药物均匀地分布到全身，不仅杀死目标细胞，还杀死健康的细胞。由于其尺寸小，配体包裹的纳米粒子(如碳纳米管、量子点、树枝状大分子等)通过配体-受体的相互作用和识别，可以有效地定向到特定的细胞类型，从而为在细胞水平上的部位特异性给药开辟了新的途径。纳米颗粒的表面和物理性质(颗粒大小、形状、拓扑、配体-受体结合亲和力等)之间的关键相互关系。他们的细胞摄取率和内吞途径将被建立。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，这项研究的成功完成将为实现基于纳米粒子的定点给药系统铺平道路。这项研究开发的计算工具随后将帮助研究界解决仅靠实验无法系统和定量探索的纳米生物界面上的其他根本重要问题。该项目将通过研究生、本科生和高中生的直接参与，为培养下一代纳米生物技术科学家和工程师提供多层次的平台。这一激动人心的研究领域的亮点将被纳入为大学生和高中生提供的专题讲座中。

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. 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. 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 this research will pave the way towards the realization of nanoparticle-based site-specific drug delivery systems. The computational tools developed from this 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.