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Nano Research 2015, 8(12): 3864-3877 https://doi.org/10.1007/s12274-015-0886-8
Research Article | Issue | Published: 13 November 2015

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

Show Author's Information Anil Khanal1,  Christopher Ullum1,  Charles W. Kimbrough2,  Nichola C. Garbett1,  Joseph A. Burlison1,  Molly W. McNally1,  Phillip Chuong1,  Ayman S. El-Baz3,  Jacek B. Jasinski3,  Lacey R. McNally1( )
Department of MedicineUniversity of LouisvilleLouisvilleKY40202USA
Department of SurgeryUniversity of LouisvilleLouisvilleKY40292USA
Speed School of EngineeringUniversity of LouisvilleLouisvilleKY40292USA
Keywords:
gold nanorods, mesoporous silica, pancreatic cancer, multispectral optoacoustic tomography, syndecan-1
Cite this article:
Khanal A, Ullum C, Kimbrough CW, et al. Tumor targeted mesoporous silica-coated gold nanorods facilitate detection of pancreatic tumors using Multispectral optoacoustic tomography. Nano Research, 2015, 8(12): 3864-3877. https://doi.org/10.1007/s12274-015-0886-8
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Abstract Full text Electronic supplementary material About this article

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 aminefunctionalized 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 PAAGNRs (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.


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Abstract
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Outline
Electronic supplementary material
About this article

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

Show Author's information Anil Khanal1, Christopher Ullum1, Charles W. Kimbrough2, Nichola C. Garbett1, Joseph A. Burlison1, Molly W. McNally1, Phillip Chuong1, Ayman S. El-Baz3, Jacek B. Jasinski3, Lacey R. McNally1( )
Department of MedicineUniversity of LouisvilleLouisvilleKY40202USA
Department of SurgeryUniversity of LouisvilleLouisvilleKY40292USA
Speed School of EngineeringUniversity of LouisvilleLouisvilleKY40292USA

Abstract

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 aminefunctionalized 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 PAAGNRs (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.

Keywords: gold nanorods, mesoporous silica, pancreatic cancer, multispectral optoacoustic tomography, syndecan-1

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Publication history
Copyright
Acknowledgements

Publication history

Received: 15 April 2015
Revised: 19 August 2015
Accepted: 25 August 2015
Published: 13 November 2015
Issue date: December 2015

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2015

Acknowledgements

Acknowledgements

This work was funded in part by the Rounsavall Foundation. C. U. was supported by the NIH R25 Cancer Education program CA 134283.

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