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

作     者：Jifen Zhang Clairissa DCorpstein Tonglei Li Jifen Zhang;Clairissa D.Corpstein;Tonglei Li

作者机构：College of Pharmaceutical SciencesSouthwest UniversityChongqing 400716China Department of Industrial and Physical PharmacyPurdue UniversityWest LafayetteIN 47907USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第4期

页      面：1021-1029页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：the financial support by the China Scholarship Council(No.201806995008,China) Key Projects of Chinese Medicine Research of Chongqing Municipal Health Bureau(ZY201701004,China) the Chao Endowment and Purdue Research Foundation for support(USA) 

主　　题：Nanocrystal Intracellular uptake Aggregation-induced emission Pharmacokinetics Tetrakis(4-hydroxyphenyl)ethylene Fate Dissolution kinetics Absorption mechanism 

摘      要：Nanocrystal formulations have been explored to deliver poorly water-soluble drug *** 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 *** this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of *** uptake studies were conducted with KB cells and characterized by confocal microscopy,fow cytometry,and quantitative *** results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved *** cellular uptake was found to be concentration-and *** addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and *** modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on frst-order ordinary differential equations(ODEs).By ftting the kinetic model against experimental measurements,it was found that the initial nanocrystal concentration had a great infuence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE *** the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the effux of THPE molecules from cells.