Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

摘要: A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters linkers and oligoamines surface modification, was synthesized evaluated regarding their structure–activity relationship gene carriers. We show that pseudodendritic core characteristics well different modifications on the influence DNA-binding ability, cytotoxicity transfection efficiency. As most promising carrier, pseudodendrimer HD O, is, OEI 800 Da modified with hexane-1,6-diol surface-modified 800 Da, identified. O exhibits efficient DNA-condensing ability to nanosized polyplexes (100–200 nm), low cytotoxicity, a degradation half-life 3 days at 37 °C physiological pH in vitro reporter gene-expression levels similar high molecular weight linear polyethylenimines (PEIs) (LPEI BPEI). In vivo studies mice reveal O/DNA upon i.v. tail-vein injection have potential for tumor tissue comparable obtained LPEI. Importantly, better tolerated than LPEI, while transgene expression more tumor-specific much lower all other investigated organs, especially lung (15 000-fold compared LPEI).