Unmodified and tyrosine-modified polyethylenimines as potential carriers for siRNA: Biophysical characterization and toxicity
International journal of pharmaceutics(2022)
摘要
Polyethylenimines (PEIs) are being explored as efficient non-viral nanocarriers for nucleic acid delivery in vitro and in vivo. To address limitations regarding PEI efficacy and biocompatibility, modifications of the chemical structure of linear and branched PEIs have been introduced, including grafting with tyrosine. The aim has been to compare linear and branched polyethylenimines of a wider range of different molecular mass with their tyrosine-modified derivatives. To do so, physico-chemical and biological properties of the polymers were investigated. Even in the absence of a negatively charged nucleic acid counterpart, PEIs form particle structures with defined size and surface potential. Tyrosine modification of PEI led to significantly reduced toxicity, while simultaneously increasing interaction with cellular membranes. All the effects were also dependent on the PEI molecular weight and structure (i.e., linear vs. branched). Especially in the case of linear PEIs, the improved membrane interaction also translated into slightly enhanced hemolysis, whereas their genotoxic potential was essentially abolished. Due to the improvement of properties critical for nano-vector efficacy and biocompati-bility, our data demonstrate that tyrosine-modified PEIs are very promising and safe nanocarriers for the delivery of small RNAs, like siRNAs and miRNAs.
更多查看译文
关键词
Polyethyleneimines,Tyrosine modification,siRNA delivery,Electrokinetic potential,Membrane fluidity,Cytotoxicity,Genotoxicity
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要