PEGylated Gold Nanoparticles Conjugated to Monoclonal F19 Antibodies as Targeted Labeling Agents for Human Pancreatic Carcinoma Tissue

被引:234
作者
Eck, Wolfgang [3 ,4 ]
Craig, Gary [1 ,2 ]
Sigdel, Aruna [1 ,2 ]
Ritter, Gerd [5 ]
Old, Lloyd J. [5 ]
Tang, Laura [6 ]
Brennan, Murray F. [7 ]
Allen, Peter J. [7 ]
Mason, Michael D. [1 ,2 ]
机构
[1] Univ Maine, Dept Chem & Biol Engn, Orono, ME 04469 USA
[2] Univ Maine, Inst Mol Biophys, Orono, ME 04469 USA
[3] Jackson Lab, Inst Mol Biophys, Bar Harbor, ME 04609 USA
[4] Heidelberg Univ, D-6900 Heidelberg, Germany
[5] Ludwig Inst Canc Res, New York, NY 10021 USA
[6] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA
[7] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA
基金
美国国家科学基金会;
关键词
targeted gold nanoparticles; heterobifunctional polyethylene glycol; F19 monoclonal antibody; pancreatic cancer; tissue labeling; darkfield microscopy;
D O I
10.1021/nn800429d
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:2263 / 2272
页数:10
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