Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery.
Polycations as one of non-viral vectors have gained increasing attentions. In this paper, polyethylenimine(PEI)-grafted polycarbonates (PMAC-g-PEIx) were synthesized as a kind of biodegradable polycations for gene delivery. Backbone polymer, poly(5-methyl-5-allyloxycarbonyl-trimethylene carbonate) (PMAC), was synthesized in bulk catalyzed by immobilized porcine pancreas lipase (IPPL). Then, PMAC-O, the allyl epoxidation product of PMAC, was further modified by PEIx with low molecular weight (x = 423, 800 and 1800). The MWs of PMAC-g-PEIx, measured by GPC-MALLS, were 81,900, 179,900 and 200,600 g/mol with polydispersities of 1.2, 1.4 and 1.7, respectively. PMAC-g-PEIx could form positively charged nano-sized particles (30-90 nm) with pDNA, and all the three PAMC-g-PEIx/DNA polyplexes had similar buffer capabilities. In vitro experiments demonstrated that the PAMC-g-PEIx showed much low cytotoxicity and enhanced transfection efficiency could be found in comparison with PEI25K in 293T cells. Furthermore, pre-incubation of PMAC-g-PEI1800 showed a weakening binding capacity with DNA. The biodegradability of PMAC-g-PEIx can facilitate the efficient release of pDNA from polyplexes and reduce cell cytotoxicity. These results suggested that PMAC-g-PEIx would be a promising non-viral biodegradable vector for gene delivery system.
Wang
Chang-Fang
CF
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China.
Lin
Yan-Xin
YX
Jiang
Tao
T
He
Feng
F
Zhuo
Ren-Xi
RX
D001672:Biocompatible Materials / Q000737:chemistry*; D001681:Biological Assay; D002021:Buffers; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D011073:Polyamines / Q000737:chemistry*; D011076:Polycarboxylate Cement / Q000737:chemistry*; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
D001672:Biocompatible Materials; D002021:Buffers; D004247:DNA; D049452:Green Fluorescent Proteins; D008156:Luciferases; D011073:Polyamines; D011076:Polycarboxylate Cement; D000071228:Polyelectrolytes; D011094:Polyethyleneimine; C005506:polycarbonate