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Silica-gold nanoshells as potential intraoperative molecular probes for HER2-overexpression in ex vivo breast tissue using near-infrared reflectance confocal microscopy

Abstract

Obtaining negative margins is critical for breast cancer patients undergoing conservation therapy in order to reduce the reemergence of the original cancer. Currently, breast cancer tumor margins are examined in a pathology lab either while the patient is anesthetized or after the surgical procedure has been terminated. These current methods often result in cancer cells present at the surgical resection margin due to inadequate margin assessment at the point of care. Due to such limitations evident in current diagnoses, tools for increasing the accuracy and speed of tumor margin detection directly in the operating room are still needed. We are exploring the potential of using a nano-biophotonics system to facilitate intraoperative tumor margin assessment ex vivo at the cellular level. By combining bioconjugated silica-based gold nanoshells, which scatter light in the near-infrared, with a portable FDA-approved reflectance confocal microscope, we first validate the use of gold nanoshells as effective reflectance-based imaging probes by evaluating the contrast enhancement of three different HER2-overexpressing cell lines. Additionally, we demonstrate the ability to detect HER2-overexpressing cells in human tissue sections within 5 min of incubation time. This work supports the use of targeted silica-based gold nanoshells as potential real-time molecular probes for HER2-overexpression in human tissue.

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Acknowledgments

We thank the Cooperative Human Tissue Network for providing fresh frozen tissue samples and Wendy Schober at MDACC for performing flow cytometry on all cell lines. This work was supported by a Department of Defense Congressionally Directed Breast Cancer Research Program Era of Hope Scholar Award to Rebekah Drezek and Tse-Kuan Yu, the Center for Biological and Environmental Nanotechnology (EEC-0118007 and EEC-0647452), and the John and Ann Doerr Fund for Computational Biomedicine.

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Correspondence to Rebekah Drezek.

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Rebekah Drezek and Tse-Kuan Yu contributed equally to this work.

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Bickford, L.R., Agollah, G., Drezek, R. et al. Silica-gold nanoshells as potential intraoperative molecular probes for HER2-overexpression in ex vivo breast tissue using near-infrared reflectance confocal microscopy. Breast Cancer Res Treat 120, 547–555 (2010). https://doi.org/10.1007/s10549-009-0408-z

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  • DOI: https://doi.org/10.1007/s10549-009-0408-z

Keywords

  • Nanoshells
  • Reflectance confocal microscopy
  • Breast cancer
  • Molecular imaging
  • Tumor margins
  • Intraoperative detection