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

Abstract 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 pl...

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Veröffentlicht in:Biomaterials 2010-01, Vol.31 (1), p.115-123
Hauptverfasser: Qiao, Yong, Huang, Yang, Qiu, Chao, Yue, Xinye, Deng, Liandong, Wan, Yanmin, Xing, Jinfeng, Zhang, Congyou, Yuan, Songhua, Dong, Anjie, Xu, Jianqing
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container_end_page 123
container_issue 1
container_start_page 115
container_title Biomaterials
container_volume 31
creator Qiao, Yong
Huang, Yang
Qiu, Chao
Yue, Xinye
Deng, Liandong
Wan, Yanmin
Xing, Jinfeng
Zhang, Congyou
Yuan, Songhua
Dong, Anjie
Xu, Jianqing
description Abstract 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. mPEG113 - b -PDMAEMA94 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.
doi_str_mv 10.1016/j.biomaterials.2009.09.032
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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. mPEG113 - b -PDMAEMA94 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.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>19781770</pmid><doi>10.1016/j.biomaterials.2009.09.032</doi><tpages>9</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Advanced Basic Science
AIDS Vaccines - administration & dosage
Animals
Cytokines - biosynthesis
Dentistry
DNA - administration & dosage
Electrophoresis, Agar Gel
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Dyes
Genes, gag
Genetic Vectors
HIV-1
HIV-1 - immunology
Human immunodeficiency virus
Immunity, Innate
Macrophages - immunology
Methacrylates - chemistry
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Mucosa
Mucous Membrane - metabolism
Nylons - chemistry
Particle Size
PDMAEMA
PEGylation
Polyethylene Glycols - chemistry
Vaccine
Vector
title 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
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