Polyaspartamide-based oligo-ethylenimine brushes with high buffer capacity and low cytotoxicity for highly efficient gene delivery.
Polyaspartamide-based oligo-ethylenimine brushes (PASP-EDA, PASP-TEPA, PASP-PEHA, and PASP-PEI 423) were synthesized from polysuccinimide (PSI) via a ring-opening reaction with N-Boc protected ethylenediamine, tetraethylenepentamine, pentaethylenehexamine, and linear polyethylenimine (Mn 423), respectively. PASP-TEPA, PASP-PEHA, and PASP-PEI 423 possess high buffer capacity between pH 5 and pH 7, which is comparable to that of branched PEI 25000. The cytotoxicity assay indicated that they all are less toxic than PEI 25000. At an N/P ratio of above 2, all of the four synthetic polycation brushes can condense plasmid DNA to form small sized (160-400 nm) polyelectrolyte complexes with positive surface charge. The transfection of HEK 293 cells with oligo-ethylenimine brush/pRE Luc polyplexes indicated that the transfection efficiencies increased with increasing the length of oligo-ethylenimine side chains. The luciferase expression with PASP-PEHA and PASP-PEI 423 were as high as or even a little higher than that of PEI 25000. The results demonstrate that polyaspartamide-based oligo-ethylenimine brushes are a very promising class of novel polycations for highly efficient and less toxic gene delivery.
Zhang
Min
M
Key Laboratory of Biomedical Polymers, Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, P.R. China.
Liu
Min
M
Xue
Ya-Nan
YN
Huang
Shi-Wen
SW
Zhuo
Ren-Xi
RX
D001388:Aziridines / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage*; D006801:Humans; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage; D011073:Polyamines / Q000737:chemistry* / Q000378:metabolism; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
D001388:Aziridines; D004247:DNA; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine; D011506:Proteins; C033132:aziridine