Modeling Particle Shape Effect in Nanomedicine

描述（由申请人提供）：纳米医学的主要挑战之一是通过设计各种形状、尺寸和材料的功能化纳米颗粒来改善纳米颗粒细胞选择性和粘附效率。最近的数据显示，非球形粒子的生物学性能明显优于球形粒子。尽管有这些令人兴奋的进展，但由于缺乏基本的理解和制造技术，非球形颗粒尚未广泛用于纳米医学应用。该研究的目的是通过多尺度建模方法揭示非球形纳米颗粒的形状依赖性粘附动力学。该提案旨在建立多尺度计算技术，用于各种环境中纳米棒/纳米盘翻滚，扩散和粘附的动态过程的基础研究。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和粘附的影响。本文的主要工作包括：（1）建立了一个三维多尺度分子-连续介质模型，用于纳米颗粒的输运和粘附动力学研究。我们最近建立的任意形状浸没结构粘附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粘附的完整动力学，其中涉及颗粒运输，扩散，翻滚，接触/粘附初始化和牢固粘附。(2)使用开发的多尺度模型来探索形状依赖的纳米颗粒靶向递送。纳米粒子的形状，尺寸，配体的密度，和流速的沉积过程中，粘附概率和沉积分布的影响将进行系统的研究。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运输和靶向功效的基础和深入了解，这将为纳米药物的设计提供新的指导，以更好地治疗疾病。

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.