Supplement to Support the Development of a New Multiplexed Imaging Tool using Raman Spectroscopy for Breast Cancer

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Project Summary Breast cancer, in particular, is very heterogeneous with many morphological and molecular features that present differently across patients. Failure to fully understand the molecular expression and tumor heterogeneity across a patient's tumor can lead to administration of ineffective therapies that increase patient morbidity and healthcare costs. The -omics era has made it possible to identify several new molecular markers involved in breast cancer development, survival, invasion and even predicting treatment response. We currently lack an easy way to obtain high content molecular information while providing high resolution spatial profiling across a patient's tumor. This proposal aims to provide physicians with an entirely new multiplexed molecular imaging strategy that has the potential to offer both high content molecular expression and spatial profiling in a single histology image. Raman spectroscopy in conjunction with surface enhanced Raman scattering (SERS) nanoparticles is an optical imaging technique that can offer unsurpassed sensitivity (on the order of fM) and multiplexing capabilities to the field of histology imaging with the potential to provide rich molecular details on the microscopic level. Clinicians will be able to utilize the imaging strategy on the same tissue sections prepared for histology. Incorporating it into the pathology workfiow could enable physicians to better understand the patient's tumor type and stratify patients to receive the most effective therapeutic regimen possible. This unique histology imaging strategy also has the potential to identify new molecular trends in patient's tissue samples that could be used to predict how aggressive their tumor is or how well the patient is likely to respond to given therapies. This innovative ex-vivo diagnostic strategy has a high likelihood for clinical translation; offering rapid whole tissue section imaging for multiple biomarkers simultaneously. Our approach begins by developing a new set of sensitive SERS nanoparticle (NP) batches, each designed with a unique spectral barcode to enable simultaneous molecular interrogation of an entire tissue sample within a single image. After fabrication and characterization of our newly developed multiplexed SERS nano particles, we will test their multiplexed imaging capabilities and tumor targeting efficiency in various breast cancer models including cell culture and on de-identified tissue sections. Our nanoparticles will actively target multiple breast cancer receptors through chemically conjugated targeting ligands. We will assess the tumor targeting efficiency of our newly developed nanoparticles with microscopic Raman imaging tools and compare with gold standard immunohistochemistry {IHC) staining. These results will be an important step in the clinical translation of this new multiplexed Raman imaging approach; to provide rapid spatial molecular profiling of a given tumor while enabling a more effective personalized therapy to the patient.