Poly(methyl methacrylate)-graft-oligoamines as low cytotoxic and efficient nonviral gene vectors.
A series of poly(methyl methacrylate)-graft-oligoamines (PMMA-g-oligoamines), including PMMA-g-DETA, PMMA-g-TETA and PMMA-g-TEPA, were synthesized through aminolysis of the PMMA with diethylenetriamine, triethylenetetramine and tetraethylenepentamine. Agarose gel retardation assay indicated that PMMA-g-oligoamines had good binding capability with plasmid DNA, and the binding capability increased with increasing length of oligoamines and content of nitrogen (N%). The results of particle size, zeta potential and morphology observation further showed that the PMMA-g-oligoamines could condense DNA efficiently and the PMMA-g-oligoamine/DNA complexes were uniform nanospheres. The in vitro cell viability indicated that PMMA-g-oligoamines were less toxic than 25 kDa PEI, though the cytotoxicity of PMMA-g-oligoamines increased slightly with increasing length of oligoamines as well as the N% of PMMA-g-oligoamines. The transfection efficiency of PMMA-g-oligoamines/DNA complexes in 293 T and HeLa cells demonstrated that PMMA-g-oligoamines could transfect cells efficiently with increasing the length of oligoamines, especially PMMA-g-TEPA with highest N%, and showed similar transfection capability as 25 kDa PEI. The cellular uptake study showed that the distribution of YOYO-1 labeled DNA in the cytoplasm and nuclei increased gradually with increasing length of oligoamines.
Wang
Yong-Qiang
YQ
Department of Chemistry, Wuhan University, Wuhan 430072, China.
Sun
Yun-Xia
YX
Hong
Xin-Lin
XL
Zhang
Xian-Zheng
XZ
Zhang
Gao-Yong
GY
D000588:Amines / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D005029:Ethylenediamines / Q000737:chemistry; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011073:Polyamines / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D014266:Trientine / Q000737:chemistry
D000588:Amines; D005029:Ethylenediamines; D011073:Polyamines; D011108:Polymers; C005391:diethylenetriamine; D019904:Polymethyl Methacrylate; D014266:Trientine; C034269:tetraethylenepentamine