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Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast
Yu Wang1, Soyoung Kang1, Altaz Khan2
1Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
Abstract:
There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast-conserving surgeries.
Insights
This study introduces a rapid molecular imaging technique using targeted nanoparticles to identify residual cancer in excised tissues. This quantitative molecular phenotyping (QMP) method aids surgeons in achieving complete tumor removal during surgery.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Nanotechnology
Background:
- Accurate tumor margin identification is crucial for complete cancer removal during surgery.
- Current methods struggle with tumor heterogeneity and require time-consuming analysis.
- Molecular imaging of cell-surface receptors offers a sensitive and specific diagnostic approach.
Purpose of the Study:
- To develop a rapid, quantitative molecular imaging technique for assessing excised tumor margins.
- To enable multiplexed detection of cancer biomarkers for improved diagnostic accuracy.
- To provide intraoperative guidance for complete tumor resection.
Main Methods:
- Topical application of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs).
- Quantitative molecular phenotyping (QMP) using a ratiometric method to distinguish specific from nonspecific NP binding.
- Validation using human tumor cell lines, xenografts, and fresh human breast tissue specimens.
Main Results:
- Demonstrated rapid (under 15 minutes) quantitative molecular phenotyping of excised tissue surfaces.
- QMP imaging results showed strong agreement with established techniques like flow cytometry and immunohistochemistry.
- The ratiometric method effectively mitigated ambiguity from nonspecific binding and uneven NP delivery.
Conclusions:
- Topical application of multiplexed SERS nanoparticles enables rapid QMP of excised tissues.
- This technique accurately identifies disease presence at tumor margins, potentially guiding intraoperative surgical decisions.
- The developed method shows promise for enhancing the efficacy of breast-conserving surgeries.
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