Tailoring of chitosans for gene delivery: novel self-branched glycosylated chitosan oligomers with improved functional properties.
作者： Sabina P. Strand , Mohamed M. Issa , Bjørn E. Christensen , Kjell M. Vårum , Per Artursson
DOI: 10.1021/BM800832U
关键词: Chitosan 、 Genetic transfer 、 Drug carrier 、 Depolymerization 、 Transfection 、 Oligomer 、 Biochemistry 、 Gene expression 、 Gene delivery 、 Chemistry
摘要: Chitosan is a promising biomaterial with an attractive safety profile; however, its application potential for gene delivery hampered by poor compatibility at physiological pH values. Here we have tailored the molecular architecture of chitosan to improve functional properties and transfer efficacy oligomers developed self-branched glycosylated oligomer (SB-TCO) substituted trisaccharide containing N-acetylglucosamine, AAM. SB-TCO was prepared controlled depolymerization chitosan, followed simultaneous branching AAM substitution. The product fully soluble complexed plasmid DNA into polyplexes high colloidal physical stability. displayed transfection in HEK293 cells, reaching efficiencies up 70%, large amounts transgene were produced. Gene confirmed HepG2 where expression levels mediated 10 4 times higher than those obtained unsubstituted linear oligomers, respectively. rapid onset both cell lines indicates efficient release transcription from polyplexes. In comparison 22 kDa PEI-based reagent used as control, possessed efficacy, significantly lower cytotoxicity, improved serum compatibility.
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