Novel hyperbranched polyamidoamine nanoparticle based gene delivery: transfection, cytotoxicity and in vitro evaluation.
In this study, hyperbranched polyamidoamine (hPAMAM) was developed as a novel non-viral gene vector for the first time. The hPAMAM was synthesized using a modified "one-pot" method. DNA was then bound to hPAMAM at different weight ratios (w(hPAMAM)/w(DNA)). The higher weight ratio could bring larger particle size and higher zeta potential of hPAMAM-DNA complexes. The encapsulated DNA was protected by hPAMAM from degradation for over 3h. Under the optimal condition, high gene transfection efficiency could be achieved in COS7 (47.47 ± 1.42%) and HEK293 (40.8 ± 0.98%) cell lines. And hPAMAM showed rather minor cytotoxicity in vitro (cell viability=91.38 ± 0.46% in COS7 and 92.38 ± 0.61% in HEK293). The hPAMAM mediated human vascular endothelial growth factor 165 (hVEGF(165)) gene transfected cells could express hVEGF(165) stably for 14 days, with the peak expression at day 2. In conclusion, hPAMAM based gene delivery was economical, effective and biocompatible, and may serve as a promising non-viral vehicle for gene therapy.
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University & Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, PR China.
Kai
K
Zhu
Changfa
C
Guo
Hao
H
Lai
Wuli
W
Yang
Chunsheng
C
Wang
D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry* / Q000633:toxicity; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D050091:Dendrimers; C104700:PAMAM Starburst; C531249:Poly(amidoamine); D011073:Polyamines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA