Modeling Particle Shape Effect in Nanomedicine

描述(申请人提供)：纳米医学的主要挑战之一是通过设计不同形状、大小和材料的功能化纳米颗粒来提高纳米颗粒的细胞选择性和黏附效率。最近关于圆柱形丝状胶束的数据开始显示，非球形粒子显著改善了球形粒子的生物学特性。尽管取得了这些令人振奋的进展，但由于缺乏基本的了解和制备技术，非球形粒子在纳米医学中的应用并不广泛。这项研究的目标是通过多尺度建模方法揭示非球形纳米颗粒的形状依赖的黏附动力学。这一建议旨在建立多尺度计算技术，以基础研究纳米棒/纳米盘在不同环境中的滚动、扩散和附着的动态过程。所提出的建模工具将有助于阐明在生理相关的流动条件下，颗粒形状对细胞靶向性和粘附性的影响。所提出的工作的主要目标是：(1)发展一个用于研究纳米颗粒传输和附着动力学的三维多尺度分子到连续介质模型。我们最近建立的任意形状浸没结构附着动力学的流体力学建模能力使我们能够首次研究非球形纳米颗粒附着的完整动力学，其中包括颗粒传输、扩散、翻滚、接触/附着初始化和牢固附着。(2)利用所建立的多尺度模型探讨了纳米颗粒的形状依赖性靶向传递。系统地研究了纳米粒子的形状、大小、配体密度和流速对沉积过程、附着概率和沉积分布的影响。公共卫生相关性：拟议的研究将导致对形状如何影响纳米药物载体的传输和靶向效果的基础和深入了解，这将为设计纳米药物以更好地治疗疾病提供新的指导。

DESCRIPTION (provided by applicant): One of the major challenges in nanomedicine is to improve nanoparticles cell selectivity and adhesion efficiency through designing functionalized nanoparticles of various shapes, sizes, and materials. Recent data on cylindrically shaped filomicelles are beginning to show non-spherical particles remarkably improved the biological properties over spherical counterpart. Despite these exciting advances, non-spherical particles have not been widely used in nanomedicine applications due to the lack of fundamental understanding and fabrication techniques. The goal of the proposed research is to uncover the shape-dependent adhesion dynamics of non- spherical nanoparticles through a multiscale modeling approach. This proposal aims to establish multiscale computational techniques for the fundamental study of the dynamic process of nanorods/nanodisks tumbling, diffusion and adhesion in various environments. The proposed modeling tool will help the elucidation of the influence of particle shape on cell targeting and adhesion under physiologically relevant flow conditions. The primary objectives of proposed work are: (1) The development of a 3D multiscale-molecular to continuum-model for the study of nanoparticle transportation and adhesion dynamics. Our recently established hydro-mechanical modeling capability for arbitrarily-shaped immersed structure adhesion dynamics enables us to study, for the first time, the full dynamics of non- spherical nanoparticle adhesion, which involves particle transportation, diffusion, tumbling, contact/adhesion initialization and firm adhesion. (2) Use the developed multiscale model to explore the shape-dependent nanoparticle targeted delivery. The influence of nanoparticle shape, size, ligand density, and flow rate on deposition process, adhesion probability, and deposition distribution will be studied systematically. PUBLIC HEALTH RELEVANCE: The proposed research will result in fundamental and indepth knowledge on how shape affects the transport and targeting efficacy of nanomedicine carriers, which will provide new guidance to the design of nanomedicine for better treatment of diseases in general.