Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence  

作　　者：Xiu Han Xiang Xu Ziheng Wu Zhenghong Wu Xiaole Qi 

机构地区：[1]Key Laboratory of Modern Chinese Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Medical School of Nanjing University,Nanjing University,Nanjing 210093,China [3]Parkville Campus,Monash University,VIC 3052,Australia

出　　处：《Acta Pharmaceutica Sinica B》2021年第10期3286-3296,共11页药学学报（英文版）

基　　金：supported by Double First-Class Innovation Team of China Pharmaceutical University(CPU2018GY40,China);National Mega-project for Innovative Drugs(2019ZX09721001,China)。

摘　　要：The functionality of DNA biomacromolecules has been widely excavated,as therapeutic drugs,carriers,and functionalized modification derivatives.In this study,we developed a series of DNA tetrahedron nanocages(Td),via synchronous conjugating different numbers of i-(X)and therapeutic siRNA on four vertexes of tetrahedral DNA nanocage(aX-Td@bsiRNA,a+b=4).This i-motif-conjugated Td exhibited good endosomal escape behaviours in A549 tumor cells,and the escape efficiency was affected by the number of i-motif.Furthermore,the downregulating mRNA and protein expression level of epidermal growth factor receptor(EGFR)caused by this siRNA embedded Td were verified in A549 cells.The tumor growth inhibition efficiency of the 2X-Td@2siRNA treated group in tumorbearing mice was significantly higher than that of non-i-motif-conjugated Td@2siRNA(3.14-fold)and free siRNA(3.63-fold).These results demonstrate a general strategy for endowing DNA nanostructures with endosomal escape behaviours to achieve effective in vivo gene delivery and therapy.

关 键 词：I-MOTIF SIRNA Gene delivery DNA tetrahedron Endosomal escape Cancer Gene silence Biocompatibility 

分 类 号：R450[医药卫生—治疗学]