Tumor targeted mesoporous silica-coated gold nanorods facilitate detection of pancreatic tumors using Multispectral optoacoustic tomography

• Published in: Nano research Vol. 8; no. 12; pp. 3864 - 3877
• Main Authors: Khanal, Anil, Ullum, Christopher, Kimbrough, Charles W., Garbett, Nichola C., Burlison, Joseph A., McNally, Molly W., Chuong, Phillip, El-Baz, Ayman S., Jasinski, Jacek B., McNally, Lacey R.
• Format: Journal Article
• Language: English
• Published: Beijing Tsinghua University Press 01.12.2015; Springer Nature B.V
• Subjects: Atomic/Molecular Structure and Spectra; Binding; Biomedicine; Biotechnology; Chemistry and Materials Science; Coating; Condensed Matter Physics; Contrast agents; Cytometry; Flow cytometry; Gold; Imaging; Insulin; Insulin-like growth factor I; Liver; Materials Science; Medical imaging; Nanoparticles; Nanorods; Nanostructure; Nanotechnology; Organs; Pancreatic cancer; Polyacrylic acid; Research Article; Silica; Silicon dioxide; Surgical implants; Syndecan; Tomography; Tumors; 介孔二氧化硅; 光声层析成像; 多光谱; 检测; 流式细胞仪; 纳米棒; 胰岛素样生长因子1; 胰腺肿瘤; multispectral optoacoustic tomography; pancreatic cancer; mesoporous silica; syndecan-1; gold nanorods
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-015-0886-8

Multispectral optoacoustic tomography （MSOT） is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the microscopic scale. While potential applications include the early detection of tumors below clinical thresholds set by current technology, the lack of tumor-specific contrast agents limits the use of MSOT imaging. Therefore, we constructed highly stable nano-contrast agents by coating gold nanorods （GNRs） with either polyacrylic acid （PAA） or amine- functionalized mesoporous silica （MS）. Syndecan-1, which has been shown to target insulin-like growth factor 1 receptor （IGF1-R） （upregulated in pancreatic tumors）, was conjugated on the surface of PAA-coated GNRs （PAA-GNRs） or MS-coated GNRs （MS-GNRs） to create tumor-targeted nanoparticles. In vitro, tumor targeting of nanoparticles was assessed with flow cytometry. In S2VP10L cells （positive for IGF1-R）, the syndecan-1 MS-GNRs （Syndecan-MS-GNRs） demonstrated an increase in OA signal, 10x, compared to syndecan-1 PAA- GNRs （Syndecan-PAA-GNRs）. Minimal binding was observed in MiaPaca-2 cells （negative for IGF1-R）. In vivo, tumor specific targeting of Syndecan-MS-GNRs was evaluated using a murine orthotopic pancreatic cancer model. The Syndecan- MS-GNRs demonstrated significantly greater accumulation within pancreatic tumors than in off-target organs such as the liver. Mice implanted with the IGF1-R negative MiaPaca-2 cells did not demonstrate specific tumor targeting. In summary, we report that targeted nano-contrast agents （Syndecan-MS-GNRs） can successfully detect orthotopic pancreatic tumors with minimum off-target binding in vivo using MSOT.