Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery. (10th March 2017)

• Record Type: Journal Article
• Authors: Zhu, Dingcheng; Yan, Huijie; Liu, Xin; Xiang, Jiajia; Zhou, Zhuxian; Tang, Jianbin; Liu, Xiangrui; Shen, Youqing
• Is Part Of: Advanced functional materials. Volume 27:Number 16(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-03-10
• Subjects: disintegrable -- gene delivery -- polysulfonium -- reactive oxygen species; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201606826
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract : Amine‐based cationic polymers have been extensively explored as nonviral carriers for gene delivery, but inefficient intracellular unpacking of polymer/DNA complexes (polyplexes) to release plasmids is still a key limiting step to high transfection efficiency. Furthermore, the amine‐resulting cationic charges in the polymer chains, and even their degraded fragments, inherently interfere with transgene expression. A cationic polymer capable of converting to uncharged fragments once inside cells would not only quickly release the DNA, but also not interfere with the gene transcription process for efficient gene expression and low toxicity. A new class of polysulfoniums that can degrade into neutral thioether fragments triggered by reactive oxygen species (ROS) is reported. The polysulfoniums condense DNA into nanosized polyplexes, which can be quickly internalized and efficiently escape from endo/lysosomes. In cancer cells, the oxidation of the boronic acid/ester by the elevated ROS levels triggers polysulfonium to break down into neutral thioether fragments, efficiently releasing DNA for gene expression. More importantly, the polyplexes have excellent serum resistance; in vivo, they efficiently deliver the suicide gene pTRAIL to intraperitoneal tumors eliciting effective anticancer activity. Abstract : A new class of reactive oxygen species (ROS)‐responsive main‐chain‐disintegrable polysulfoniums, which respond to the elevated intracellular ROS and degrade into neutral thioether fragments is reported. They can not only quickly release the carried DNA but also avoid interference with the gene transcription process, leading to efficient gene expression and low toxicity.