2017-11-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/692328摘要：近年來，功能性奈米粒子在標靶治療中已被廣泛地使用。由於其高複雜度，在製造與臨床中常耗費可觀的資源。透過多尺度計算模擬，我們將可預測在不同環境中，如何有效地將奈米粒子與負載藥物運送到目的地。本計畫將融合基本的統計力學與膠體流體力學理論，來探究在特定生化結合作用(如:抗體—抗原)的影響下，具有不同表面修飾與官能基的功能性奈米粒子在細胞周圍的自組裝現象以及其與細胞結合之動力行為。在第二年裡，我們將結合蒙地卡羅法與分子動力學，發展多尺度分子模擬平台，以探討具有複雜結構或形狀的奈米粒子在細胞周圍與表面蛋白質(抗原)的交互作用。<br> Abstract: Drug delivery using targeted nanoparticles is a potent application of nanotechnology to treat disease. Owing to the high-dimensional parameter space involved, targeted nanoparticle design and medical use are amenable to multiscale computational modeling to provide predictive values of appropriate characteristics for manufacture and clinical application while reducing the time, expense, and other resources necessary for otherwise large scale experimentation. In the past 3 years, Web of Science keyword “functionalized nanoparticle” search return 2481 publications. However, the published literature for associated theoretical/computational aspects of nanoparticle-based targeted drug delivery remains limited. This suggests that a physiologically sound, theoretically robust, and computationally tractable model is critical for rational design of nanoparticles for drug delivery. In this project, we propose combining fundamental principles of statistical mechanics and colloidal hydrodynamics to tackle the design of surface-functionalized nanoparticles that can self-assemble and bind to the target cells. In order to study ligand-functionalized nanoparticles with more complex architectures or anisotropic shapes, and capture the diffusion of receptors on the cell surface that interact with the ligands, in Year 2, we will develop a multiscale molecular simulation framework that is capable of incorporating the molecular details in the nanoparticle model and predicting transient dynamics spanning a wide spectrum of time scales. Through interfacing with biophysicists and chemists, the nanoparticle design working table with suitable model parameters for various medical applications will be constructed throughout the investigation.統計力學流體力學多尺度模擬標靶藥物傳遞功能性奈米粒子statistical mechanicshydrodynamicsmultiscale modelingtargeted drug deliveryfunctionalized nanoparticles