表面修飾之複合奈米粒子與細胞結合動力學之理論模擬

Abstract

表面高分子修飾之複合奈米粒子 (polymer-grafted stealth nanoparticle) 由於可降低免疫系統識別與巨噬細胞吞噬之機率，因此作為標靶藥物之載體具有非常大的優勢。雖然許多研究發表已證實其在血液中的循環時間明顯優於其他載體，但較少文獻著墨於表面修飾後之複合奈米粒子在靠近血管內皮，與細胞表面受體結合時的動力學行為。本研究使用朗之萬方程式作為主導方程式，模擬當此種奈米粒子靠近血管壁，在同時受到流體阻力、熱擾動、配體-受體結合、嫁接高分子隨時間之形變與細胞膜型態影響的情形下，於細胞表面吸附的暫態行為。透過分析均方位移、粒子速度之自相關函數與粒子位置之自相關函數，本研究顯示複合奈米粒子的動力學行為主要為兩力交互作用的結果：流體作用於粒子表面之作用力，以及配體-受體結合時的吸引力。此外，粒子的暫態行為產生明顯變化時的特徵時間亦可作為此一論點之佐證。透過分析粒子速度與位置之自相關函數、嫁接高分子鏈位移之自相關函數與位移機率分布，本研究顯示中心粒子運動行為主要受到嫁接高分子主導。細胞膜型態則是會影響配體-受體結合所產生的位能井，因而改變嫁接高分子之形變運動。

The polymer-grafted stealth nanoparticles are promising materials for nanocarriers in vascular targeted drug delivery due to their capability of avoiding the recognition by the immune system. Although the long-circulation time of the SNP can be generally achieved, the delivery efficiency of such nanoparticles is also influenced by various physiological factors such as vessel-wall-mediated hydrodynamic interactions, biological recognition between its targeting agents and membrane receptors, as well as cell membrane morphology. In this work, we model the SNP as a composite nanoparticle consisting of a hard core coated with a porous polymeric brush with end-ligands and theoretically investigate its adhesive dynamics to the cell surface using a stochastic Langevin framework. The annulus model is applied to characterize the hydrodynamic properties of the SNP. We demonstrate that the structure of the SNP and the relaxation behavior of the grafted polymer have substantial effect on the temporal motion of the SNP. Also, the interplay between the thermodynamic effects and hydrodynamic interactions substantially impacts the transient relaxation of both the velocity and position of the SNP, as evidenced by the distinct behaviors observed at different characteristic time scales.