Abstract
Cell surface marker expression in tumors dictates the selection of therapeutics, therapy response, and survival. However, biopsies are invasive, sample only a small area of the tumor landscape and may miss significant areas of heterogeneous expression. Here, we investigated the potential of antibody-conjugated surface-enhanced resonance Raman scattering nanoparticles (SERRS-NPs) to depict and quantify high and low tumoral surface marker expression, focusing on the surface markers epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in an intracerebral and peripheral setting with an inter-and intratumoral comparison of Raman signal intensities. Methods: ICR-Prkdc <scid> mice were injected with glioblastoma, epidermoid carcinoma, or breast tumor cell lines intracerebrally and peripherally. SERRS-NPs were functionalized with cetuximab or trastuzumab and administered via tail vein injection. Raman imaging was performed 18 hours post-injection in excised tumors and in vivo through the skull. Tumors were then fixed and processed for immunohistochemical evaluation. Results: Confirmed by MRI and immunohistochemistry for EGFR and HER2, our results demonstrate that antibody-conjugated SERRS-NPs go beyond the delineation of a tumor and offer clear and distinct Raman spectra that reflect the distribution of the targeted surface marker. The intensity of the SERRS-NP signal accurately discriminated high-versus low-expressing surface markers between tumors, and between different areas within tumors. Conclusion: Biopsies can be highly invasive procedures and provide a limited sample of molecular expression within a tumor. Our nanoparticle-based Raman imaging approach offers the potential to provide non-invasive and more comprehensive molecular imaging and an alternative to the current clinical gold standard of immunohistochemistry.
Original language | English (US) |
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Pages (from-to) | 256-269 |
Number of pages | 14 |
Journal | Nanotheranostics |
Volume | 6 |
Issue number | 3 |
DOIs | |
State | Published - 2021 |
Keywords
- Brain tumor
- Breast Cancer
- Breast Cancer Metastasis
- EGFR
- Glioblastoma multiforme
- HER2
- Raman Nanoparticles
- Raman Spectroscopy
- Raman imaging
- SERRS
- Surface marker expression
- Tumor Heterogeneity
ASJC Scopus subject areas
- Biotechnology
- Medicine (miscellaneous)
- Biomedical Engineering
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)