Nonviral gene carriers based on diblock copolymers of poly(2-ethyl-2-oxazoline) and linear polyethylenimine.
Diblock copolymers that consist of poly(2-ethyl-2-oxazoline) (PEOz) and linear polyethylenimine (LPEI) were prepared for use as nonviral gene carriers. The PEOz-b-LPEI copolymers were synthesized by coupling PEOz with LPEI in a thiol-disulfide exchange reaction between the sulfhydryl and pyridyl disulfide terminal groups. A polymer/DNA weight ratio (P/D) of over 12 was required to enable PEOz-b-LPEI to condense DNA completely. The DNA-condensing capability of the diblock copolymers was increased with increasing the hydrolytic degrees of the LPEI segment. The PEOz-b-LPEI polyplexes were stable in 150 mM NaCl aqueous solution and had a mean diameter around 190 nm, whereas BPEI and LPEI polyplexes formed large aggregates in the range 300-500 nm. In addition, these polyplexes exhibited the sensitivity to solution pH and were dissociated in the acidic buffers (pH < or = 5.5). The results of in vitro cell viability and luciferase assay indicated that PEOz-b-LPEI showed not only low cytotoxicity but also high transfection efficiency in gene expression.
Hsiue
Ging-Ho
GH
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300 Taiwan, ROC. ghhsiue@ che.nthu.edu.tw
Chiang
Hou-Zen
HZ
Wang
Chau-Hui
CH
Juang
Tzuoh-Min
TM
D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D010316:Particle Size; D011073:Polyamines; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection
D004279:DNA, Viral; D010080:Oxazoles; D011073:Polyamines; D011108:Polymers; C511916:poly(2-ethyl-2-oxazoline); D011094:Polyethyleneimine