Poly(2-aminoethyl methacrylate) with well-defined chain length for DNA vaccine delivery to dendritic cells.
Poly(2-aminoethyl methacrylate) with well-defined chain length for DNA vaccine delivery to dendritic cells.
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DOI：
10.1021/bm201360v
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发表时间：
2011-12-12
影响因子：
6.2
通讯作者：
Wang, Chun
中科院分区：
文献类型：
--
作者：
Ji, Weihang;Panus, David;Palumbo, R. Noelle;Tang, Rupei;Wang, Chun
采用原子转移自由基聚合（ATRP）技术合成了具有明确链长和窄分子量分布的聚（2-氨基乙基甲基丙烯酸酯）（PAEM）均聚物，并对PAEM/质粒DNA多聚物的胶体特性、多聚物在抗原提呈树突状细胞（dc）中的吸收和亚细胞转运，以及PAEM作为潜在DNA疫苗载体的生物学性能进行了综合研究。不同链长（45、75和150重复单位）的PAEM在将质粒DNA凝聚成狭窄分散的纳米颗粒方面表现出不同的强度，并且具有非常低的细胞毒性。较长的聚合物链长度导致质粒DNA的整体细胞摄取和核摄取水平较高，但较短的聚合物链有利于胞内和核内自由质粒从多聚体释放。尽管其化学结构简单，但PAEM在体外有或无血清的培养基中都能非常有效地转染DCs，并导致DCs表型成熟。当使用模型抗原编码卵清蛋白质粒时，转染的dc刺激naïve CD8+ T细胞的激活，产生高水平的干扰素-γ。转染、DC成熟和CD8+ T细胞活化的效率表现出不同程度的聚合物链长度依赖性。这些结构明确的阳离子聚合物可能有很大的潜力作为有效的DNA疫苗载体和免疫刺激佐剂。它们也可以作为模型材料系统，用于阐明聚合物介导的DNA疫苗递送的结构和细胞内机制。
Poly(2-aminoethyl methacrylate) (PAEM) homopolymers with defined chain-length and narrow molecular weight distribution were synthesized using atom transfer radical polymerization (ATRP), and a comprehensive study was conducted to evaluate the colloidal properties of PAEM/plasmid DNA polyplexes, the uptake and subcellular trafficking of polyplexes in antigen-presenting dendritic cells (DCs), and the biological performance of PAEM as a potential DNA vaccine carrier. PAEM of different chain-length (45, 75 and 150 repeating units) showed varying strength in condensing plasmid DNA into narrowly dispersed nanoparticles with very low cytotoxicity. Longer polymer chain-length resulted in higher levels of overall cellular uptake and nuclear uptake of plasmid DNA, but shorter polymer chains favored intracellular and intra-nuclear release of free plasmid from the polyplexes. Despite its simple chemical structure, PAEM transfected DCs very efficiently in vitro in media with or without serum and led to phenotypic maturation of DCs. When a model antigen-encoding ovalbumin plasmid was used, transfected DCs stimulated the activation of naïve CD8+ T cells to produce high levels of interferon-γ. The efficiency of transfection, DC maturation, and CD8+ T cell activation showed varying degrees of polymer chain-length dependence. These structurally defined cationic polymers may have much potential as efficient DNA vaccine carriers and immunostimulatory adjuvants. They may also serve as a model material system for elucidating structural and intracellular mechanisms of polymer-mediated DNA vaccine delivery.
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DOI：
10.1016/j.jconrel.2011.08.037
发表时间：
2012-01-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Palumbo RN;Zhong X;Wang C
通讯作者：
Wang C
影响因子：
6.2
作者：
Dubruel, P;Christiaens, B;Schacht, E
通讯作者：
Schacht, E
影响因子：
5.1
作者：
Dash, PR;Read, ML;Seymour, LW
通讯作者：
Seymour, LW
影响因子：
12.4
作者：
Greenland, JR;Liu, HN;Letvin, NL
通讯作者：
Letvin, NL
影响因子：
2.8
作者：
Kuo, JHS
通讯作者：
Kuo, JHS