Modeling the gene delivery process of the needle array-based tissue nanotransfection  

作　　者：Zhigang Li Yi Xuan Subhadip Ghatak Poornachander RGuda Sashwati Roy Chandan K.Sen 

机构地区：[1]Indiana Center for Regenerative Medicine and Engineering,Indiana University Health Comprehensive Wound Center,Department of Surgery,Indiana University School of Medicine,Indianapolis,IN 46202,USA [2]Birck Nanotechnology Center and Weldon School of Biomedical Engineering,Purdue University,West Lafayette,IN 47907,USA

出　　处：《Nano Research》2022年第4期3409-3421,共13页纳米研究（英文版）

基　　金：This work was supported in part by National Institutes of Health(NIH)grant(No.DK128845);Department of Defense grant(Nos.W81XWH-21-1-0097,W81XWH-21-1-0033,and W81XWH-20-1-251)to C.K.S,NIH grant(No.GM143572)to Y.X,and NIH grant(No.DK129592)to S.G.

摘　　要：Hollow needle array-based tissue nanotransfection(TNT)presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric pulses.In this work,the gene delivery process of TNT was simulated and experimentally validated.We adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin structure.The distribution of nonuniform electric field across the skin results in various electroporation behavior for each cell.Cells underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric field.The percentage of electroporated cells within the skin structure,with pore radius over 10 nm,increases from 25%to 82%as the applied voltage increases from 100 to 150 V/mm.Furthermore,the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based model.The delivery distance increased nonlinearly as the applied voltage and pulse number increased,which mainly depends on the diffusion characteristics and electric conductivity of each layer.It was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery depth.This work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings.

关 键 词：tissue nanotransfection silicon needle array hollow needle array ELECTROPORATION ELECTROPHORESIS gene delivery 

分 类 号：R318[医药卫生—生物医学工程]