Improving gene delivery efficiency of bioreducible poly(amidoamine)s via grafting with dendritic poly(amidoamine)s.
Dendritic poly(amidoamine)s (PAMAM)s were introduced into the side chains of disulfide-containing poly(amidoamine)s via repetitive Michael addition and amidation. The bioreducible poly(amidoamine)s grafted with dendritic polyamidoamines showed high buffer capacity, low cytotoxicity and strong DNA binding ability at low N/P ratio. They were able to condense DNA into small sized polycation/DNA complexes, which degraded and released the incorporated DNA under reductive conditions. In comparison to the original disulfide-containing poly(amidoamine) with aminoethyl side chain, the grafting of the bioreducible poly(amidoamine) with dendrimer greatly improved the transfection efficiencies of 293T and HeLa cells with foreign DNA at various N/P ratios. The structure-gene delivery property relations of dendrimer-grafted polycations will provide valuable insight into the design of highly efficient and less toxic polycationic gene carriers.
Xue
Ya-Nan
YN
Key Laboratory of Biomedical Polymers, Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Liu
Min
M
Peng
Lin
L
Huang
Shi-Wen
SW
Zhuo
Ren-Xi
RX
D002021:Buffers; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D004996:Ethidium / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044967:Serum / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014162:Transfection / Q000379:methods
D002021:Buffers; D050091:Dendrimers; D004220:Disulfides; C104700:PAMAM Starburst; C531249:Poly(amidoamine); D011073:Polyamines; D049452:Green Fluorescent Proteins; D004247:DNA; D008156:Luciferases; D004996:Ethidium; D004229:Dithiothreitol