Intracellular uptake of nanocrystals:Probing with aggregation-induced emission of fluorescence and kinetic modeling

• 作者: Jifen Zhang Clairissa D.Corpstein Tonglei Li
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original articles
• 页码范围: 1021-1029
• 页数: 9页
• 语种: 英文

摘要

Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole body.In this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracel-lular absorption mechanism and dissolution kinetics of nanocrystals.Cellular uptake studies were con-ducted with KB cells and characterized by confocal microscopy,flow cytometry,and quantitative analyses.The results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved molecules.The cellular uptake was found to be concentration-and time-dependent.In addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and nanocrystals.Kinetic modeling was conducted to further understand the cellular mecha-nism of THPE nanocrystals based on first-order ordinary differential equations(ODEs).By fitting the ki-netic model against experimental measurements,it was found that the initial nanocrystal concentration had a great influence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE na-nocrystals.As the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the efflux of THPE molecules from cells.