The use of PEGylated poly [2-(N,N-dimethylamino) ethyl methacrylate] as a mucosal DNA delivery vector and the activation of innate immunity and improvement of HIV-1-specific immune responses.
To minimize the cytotoxicity of poly (2-(dimethylamino) ethyl methacrylate) (PDMAEMA) as a gene delivery vector, we synthesized PEGylated PDMAEMA by atom transfer radical polymerization (ATRP). Here we report its effects on transfection efficiency in vitro delivered with a GFP expression plasmid and immunogenicity in vivo after complexed with a HIV gag gene DNA vaccine. mPEG(113)-b-PDMAEMA(94) was efficient in condensing DNA and formed polyplexes with an average diameter of about 150 nm. The in vitro transfection experiments demonstrated that PEGylation dramatically decreased the cytotoxicity at the N/P ratios above 30, although the transfection efficiency in vitro was reduced. Interestingly, mice in vivo vaccination study clearly showed that PEGylated PDMAEMA used as DNA delivery vector significantly improved the prime effect of DNA vaccine through intranasal administration. Importantly, PEGylated PDMAEMA was further proved its ability to induce cytokines production by murine macrophages. Overall, mPEG-b-PDMAEMA can be used as an efficient DNA vaccine vector which enhances adaptive immune responses by activating innate immunity.
Qiao
Yong
Y
School of Material Science and Engineering, Tianjin University, Tianjin 300072, China.
Huang
Yang
Y
Qiu
Chao
C
Yue
Xinye
X
Deng
Liandong
L
Wan
Yanmin
Y
Xing
Jinfeng
J
Zhang
Congyou
C
Yuan
Songhua
S
Dong
Anjie
A
Xu
Jianqing
J
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000008:administration & dosage*; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005456:Fluorescent Dyes; D015750:Genes, gag; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D009092:Mucous Membrane / Q000378:metabolism*; D009757:Nylons / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*
D016915:AIDS Vaccines; D016207:Cytokines; D005456:Fluorescent Dyes; D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D011092:Polyethylene Glycols; D004247:DNA