A reactive oxygen species-responsive dendrimer with low cytotoxicity for efficient and targeted gene delivery  

作　　者：Yueqi Wang Changjian Li Libo Du Yang Liu 

机构地区：[1]State Key Laboratory for Structural Chemistry of Unstable and Stable Species,Center for Molecular Science,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China [2]Graduate School,University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Chinese Chemical Letters》2020年第1期275-280,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos.31571020,31570856 and 31300697)

摘　　要：Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene ca rriers with high delivery efficiency and low cytotoxicity has long been a key project.Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics.However,when they are used as gene carrier,the gene transfection efficiency is not satisfactory.Herein,a novel thioketal-core polyamidoamine dendrimer(i.e.,ROS-PAMAM)was synthesized and characterized.Compared to ethylenediamine-core dendrimers or widely used cationic polymers of polyetherimide,ROS-PAMAM showed lower cytotoxicity.Moreover,ROS-PAMAM demonstrated reactive oxygen species responsive characteristics,which can facilitate the release of siRNA in the tumor microenvironment.In vitro gene transfection experiments based on A549 cells confirmed that siRNA/ROS-PAMAM exhibits high gene transfection efficiency.It is concluded that ROS-PAMAM shows great potential as a generalizable vehicle for gene therapy applications.Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene ca rriers with high delivery efficiency and low cytotoxicity has long been a key project.Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics.However,when they are used as gene carrier,the gene transfection efficiency is not satisfactory.Herein,a novel thioketal-core polyamidoamine dendrimer(i.e.,ROS-PAMAM) was synthesized and characterized.Compared to ethylenediamine-core dendrimers or widely used cationic polymers of polyetherimide,ROS-PAMAM showed lower cytotoxicity.Moreover,ROS-PAMAM demonstrated reactive oxygen species responsive characteristics,which can facilitate the release of siRNA in the tumor microenvironment.In vitro gene transfection experiments based on A549 cells confirmed that siRNA/ROS-PAMAM exhibits high gene transfection efficiency.It is concluded that ROS-PAMAM shows great potential as a generalizable vehicle for gene therapy applications.

关 键 词：DENDRIMER Reactive oxygen species Cancer Gene therapy Low cytotoxicity 

分 类 号：R450[医药卫生—治疗学] TQ317[医药卫生—临床医学]