PEGylated PEI-based biodegradable polymers as non-viral gene vectors.
Novel functional biodegradable gene vectors, poly(L-succinimide)-g-polyethylenimines-g-poly(ethylene glycol) (PSI-g-PEI-g-PEGs) were synthesized by conjugating methoxy poly(ethylene glycol) (mPEG, M(w)=750 Da) to PEI segments (M(w)=800 Da) of PSI-g-PEI. The physicochemical properties of PSI-g-PEI-g-PEGs, including buffering capability, pDNA binding ability, cytotoxicity, zeta potential and the particle size of polymer/pDNA complexes, were explored. The influence of PEGylation was discussed based on a comparative study of PSI-g-PEI-g-PEGs, PSI-g-PEI and PEI25k (M(w)=25 kDa). SEM images revealed that PSI-g-PEI-g-PEG/pDNA particles have a regular shape with the diameter ranging from 70 to 170 nm. PEGylation could suppress the aggregation occurrence between complexes, resulting in a reduction of the polymer/pDNA complex size. PSI-g-PEI-g-PEGs exhibited remarkably lower cytotoxicity compared to PSI-g-PEI and PEI25k. In 293T and HeLa cells, the obtained PSI-g-PEI-g-PEGs showed very high transfection efficiency compared to PEI25k. Fluorescent confocal microscopy demonstrated that PSI-g-PEI-g-PEGs could effectively transport pGL-3 plasmids into the nuclei of HeLa cells. Taking into account the continued high transfection efficacy and decreased toxicity after PEG modification, PSI-g-PEI-g-PEGs show great potential as the non-viral vectors for gene transfection.
Huang
Fu-Wei
FW
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Wang
Hui-Yuan
HY
Li
Cao
C
Wang
Hua-Fen
HF
Sun
Yun-Xia
YX
Feng
Jun
J
Zhang
Xian-Zheng
XZ
Zhuo
Ren-Xi
RX
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002021:Buffers; D016923:Cell Death / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D017186:Titrimetry; D014162:Transfection; D014780:Viruses / Q000235:genetics
D001672:Biocompatible Materials; D002021:Buffers; C485184:enhanced green fluorescent protein; C554825:polysuccinimide-graft-polyethylenimine-graft-poly(ethylene glycol); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D008156:Luciferases