Design and synthesis of multifunctional gold nanoparticles bearing tumor-associated glycopeptide antigens as potential cancer vaccines.
Design and synthesis of multifunctional gold nanoparticles bearing tumor-associated glycopeptide antigens as potential cancer vaccines.
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具有肿瘤相关糖肽抗原作为潜在癌症疫苗的多功能金纳米颗粒的设计和合成。
DOI：
10.1021/bc200606s
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发表时间：
2012-08-15
影响因子：
4.7
通讯作者：
Barchi, Joseph J., Jr.
中科院分区：
文献类型：
--
作者：
Brinas, Raymond P.;Sundgren, Andreas;Sahoo, Padmini;Morey, Susan;Rittenhouse-Olson, Kate;Wilding, Greg E.;Deng, Wei;Barchi, Joseph J., Jr.
针对特定类型癌症的疫苗的开发将为治疗干预提供新的方式。在这里，我们描述了由核心直径为 3-5 nm 的球形金纳米粒子制备的新型疫苗结构的合成。这些颗粒涂有肿瘤相关糖肽抗原，其中包含细胞表面粘蛋白 MUC4，并在不同位点附着有 Thomsen Friedenreich (TF) 抗原，以及来自补体衍生蛋白 C3d 的 28 个残基肽，充当 B 细胞激活“分子佐剂”。该合成需要固相糖肽合成、适当连接体的设计以及各种分子与颗粒的附着化学。与金表面的附着是由一种新型的含硫醇 33 原子连接体介导的，该连接体经过进一步修饰，可作为第三个“间隔”组分包含在几种三组分疫苗平台的合成中。几组小鼠用一种纳米平台构建体或无抗原涂层的对照颗粒进行疫苗接种。在针对每种糖肽抗原的酶免疫测定 (EIA) 中对来自免疫动物的血清进行的评估显示出较小但具有统计学意义的免疫反应，同时产生 IgM 和 IgG 同种型。含有一种碳水化合物抗原（B、C 和 E）的疫苗比含有两种连续二糖（D）的疫苗产生更强烈的反应，并且在肽的第 10 位上连接有苏氨酸的 TF 抗原的疫苗 E 被选择用于 IgG 而不是 IgM，这表明同种型转换。数据表明该平台可能是肿瘤相关糖肽抗原的可行递送系统。
The development of vaccines against specific types of cancers will offer new modalities for therapeutic intervention. Here we describe the synthesis of a novel vaccine construction prepared from spherical gold nanoparticles of 3–5 nm core diameters. The particles were coated with both the tumor-associated glycopeptides antigens containing the cell-surface mucin MUC4 with Thomsen Friedenreich (TF) antigen attached at different sites and a 28-residue peptide from the complement derived protein C3d to act as a B-cell activating “molecular adjuvant”. The synthesis entailed solid phase glycopeptide synthesis, design of appropriate linkers and attachment chemistry of the various molecules to the particles. Attachment to the gold surface was mediated by a novel thiol-containing 33 atom linker which was further modified to be included as a third “spacer” component in the synthesis of several three-component vaccine platforms. Groups of mice were vaccinated either with one of the nanoplatform constructs or with control particles without antigen coating. Evaluation of sera from the immunized animals in enzyme immunoassays (EIA) against each glycopeptide antigen showed a small but statistically significant immune response with production of both IgM and IgG isotypes. Vaccines with one carbohydrate antigen (B, C and E) gave more robust responses than the one with two contiguous disaccharides (D), and vaccine E with a TF antigen attached to threonine at the 10th position of the peptide was selected for IgG over IgM suggesting isotype switching. The data suggested that this platform may be a viable delivery system for tumor-associated glycopeptide antigens.
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影响因子：
16.6
作者：
Dziadek, S;Kowalczyk, D;Kunz, H
通讯作者：
Kunz, H
影响因子：
4.8
作者：
Heimburg, Jamie;Yan, Jun;Rittenhouse-Olson, Kate
通讯作者：
Rittenhouse-Olson, Kate
影响因子：
4.3
作者：
Dziadek, S;Brocke, C;Kunz, H
通讯作者：
Kunz, H
DOI：
10.1039/c39950001655
发表时间：
1995-08-21
影响因子：
--
作者：
BRUST, M;FINK, J;KIELY, C
通讯作者：
KIELY, C
影响因子：
16.6
作者：
Dziadek, S;Hobel, A;Kunz, H
通讯作者：
Kunz, H