PEGylated Gold Nanoparticles Conjugated to Monoclonal F19 Antibodies as Targeted Labeling Agents for Human Pancreatic Carcinoma Tissue
PEGylated Gold Nanoparticles Conjugated to Monoclonal F19 Antibodies as Targeted Labeling Agents for Human Pancreatic Carcinoma Tissue
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DOI：
10.1021/nn800429d
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发表时间：
2008-11-01
期刊：
影响因子：
17.1
通讯作者：
Mason, Michael D.
中科院分区：
文献类型：
--
作者：
Eck, Wolfgang;Craig, Gary;Mason, Michael D.
在这项研究中，我们描述了对与手术切除的人胰腺癌组织结合的抗体偶联纳米颗粒的光学检测。使用约15纳米的球形金核制备了由异双功能聚乙二醇（PEG）稳定的金纳米颗粒，并将其与F19单克隆抗体共价偶联。异双功能PEG配体包含一个用于稳定锚定在金表面的二硫醇基团和一个用于将抗体偶联到PEG外壳外部的末端羧基。纳米颗粒 - 抗体生物偶联物形成高度稳定的分散体，并表现出对团聚的长期抗性。这已通过动态光散射、尺寸排阻色谱和透射电子显微镜得到证明。纳米颗粒生物偶联物被用于标记切除的人胰腺腺癌约5微米厚切片中的肿瘤间质。在冲洗掉未结合的纳米颗粒并固定后，通过暗场显微镜在纳米颗粒共振散射最大值（约560纳米）附近对组织样本进行成像。这些图像显示出明显的组织特征，并表明这种新型标记方法可以方便地识别癌组织。用与非特异性对照抗体偶联的金纳米颗粒处理的肿瘤样本以及用mAb - F19偶联的金纳米颗粒处理的非癌性胰腺组织都显示出正确的阴性结果，且没有组织染色。
In this study, we describe optical detection of anti body-conjugated nanopartides bound to surgically resected human pancreatic cancer tissue. Gold nanoparticles; stabilized by heterobifunctional polyethylene glycol (PEG) were prepared using similar to 15 nm spherical gold cores and covalently coupled to F19 monoclonal antibodies. The heterobifunctional PEG ligands contain a dithiol group for stable anchoring onto the gold surface and a terminal carboxy group for coupling of antibodies to the outside of the PEG shell. The nanoparticle-antibody bioconjugates form highly stable dispersions and exhibit long-term resistance to agglomeration. This has been demonstrated by dynamic light scattering, size exclusion chromatography, and transmission electron microscopy. The nanoparticle bioconjugates were used to label tumor stroma in approximately 5 mu m thick sections of resected human pancreatic adenocarcinoma. After rinsing away nonbound nanoparticles and fixation, the tissue samples were imaged by darkfield microscopy near the nanoparticle resonance scattering maximum (similar to 560 nm). The images display pronounced tissue features and suggest that this novel labeling method could provide for facile identification of cancer tissue. Tumor samples treated with gold nanoparticles conjugated to nonspecific control antibodies and noncancerous pancreatic tissue treated with mAb-F19-conjugated gold nanoparticles both exhibited correctly negative results and showed no tissue staining.