Alginate-graft-PEI as a gene delivery vector with high efficiency and low cytotoxicity.
To overcome the efficiency-cytotoxicity dilemma of native PEI and incorporate the advantages of alginate, we designed a novel gene vector by grafting PEI 2000 onto alginate, an anionic polysaccharide with excellent biocompatibility. The alginate-graft-PEI (Alg-g-PEI) was successfully  synthesized and then characterized by elemental analysis, (1)H-NMR and (13)C-NMR. The M(w) of Alg-g-PEI is ca. 17 000. Acid-base titration confirmed that Alg-g-PEI retained the buffering capacity of native PEI. The DNA binding ability of the polymer  was confirmed by gel retardation assay. DSL analysis showed that Alg-g-PEI had a particle size and zeta-potential similar to PEI 25K. AFM detected a clear and well-shaped morphology of the complexes. Additionally, Alg-g-PEI exhibited lower cytotoxicity than PEI 25K in BEL7402, MSC and RVMSC  cells. Compared with PEI 25K, Alg-g-PEI had comparable or even higher transfection efficiency. Similarly, Alg-g-PEI-mediated VEGF expression was significantly higher compared with PEI 25K-mediated VEGF expression. All together, our results suggest that Alg-g-PEI has a potential to be a safe  and efficient agent for gene therapy.
Key Laboratory on Assisted Circulation, Ministry of Health, First Affiliated Hospital, Sun Yat-sen University, Guangdong 510089, P. R. China.
Wen
W
He
Zhenhuan
Z
Guo
Yuting
Y
Wen
Qian
Q
Wang
Bimei
B
Xie
Shaofang
S
Zhu
Qinmei
Q
Wang
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002021:Buffers; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011094:Polyethyleneimine / Q000737:chemistry*; D011817:Rabbits; D014162:Transfection / Q000379:methods*
D000464:Alginates; D002021:Buffers; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D011094:Polyethyleneimine; D004247:DNA