Abstract

Effective treatment of patients with malignant brain tumors requires surgical resection of a high percentage of the bulk tumor. Surgeons require a method that enables delineation of tumor margins, which are not visually distinct by eye. In this study, the feasibility of using gold nanorods (GNRs) for this purpose is evaluated. Anti-Epidermal Growth Factor Receptor (anti-EGFR) conjugated GNRs are used to label human xenograft glioblastoma multiforme (GBM) tumors embedded within slices of brain tissues from healthy nude mice. The anti-EGFR GNRs exhibit enhanced absorption at red to near-infrared wavelengths, often referred to as the tissue optical window, where absorption from blood is minimal. To enable definition of molecular specificity and spatial accuracy of the label, the GNR absorption is compared with GFP fluorescence which is expressed by the GBM cells used here. This work demonstrates a simple but highly translational technique to classify normal and malignant brain tissue regions in open surgery applications using immunolabeled GNR contrast agents.

Highlights

  • Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor [1]

  • We propose the novel use of immunolabeled plasmonic gold nanoparticles (GNPs) as molecular contrast agents for brain tumor delineation

  • While longer nanorods exhibit similar absorption in the NIR range, contrast in the visible range is preferable as it may be more understood by a surgeon observing gold nanorods (GNRs) labeled tissues, especially if a color CCD is utilized in a clinical system

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Summary

Introduction

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor [1]. The World Health Organization (WHO) has classified GBM as a class IV malignancy [2]. This classification refers to the tumor’s high rate of proliferation, increased angiogenesis, invasiveness into the surrounding tissues, and fatal outcome. The median prognosis for patients diagnosed with GBM is approximately 12 months, while the five-year survival rate for this disease is only 4% [4]. The poor prognosis associated with GBM is a direct effect of the tumor’s diffuse proliferation along with its resistance to traditional treatments [5,6]

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