期刊
NANOTECHNOLOGY
卷 28, 期 46, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/1361-6528/aa8c9c
关键词
gene delivery vector; cytotoxicity; endocytic uptake mechanism; lysosomal degradation; amphiphilic beta-cyclodextrin derivatives
资金
- National Natural Science Foundation of China [21342017]
- Excellent Young Talents Support Program
- Science & Technology Fund Planning Project of Fourth Military Medical University [2016XC078]
The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic beta-cyclodextrin (beta-CD) derivatives were designed and synthesized by using 6-mono-OTs-beta-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of beta-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed beta-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.
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