Project Summary
The first line of treatment for several cancer patients is surgical debulking which can suffer from poor tumor
localization resulting in lengthy incomplete surgeries and repeat visits. Our objective is to provide physicians with
an entirely new multimodal molecular imaging strategy that has the potential to offer 1) intra-operative surgical
guidance to ensure complete resection of the tumor, and 2) post-operative molecular expression information to
improve therapeutic decision-making. Oral squamous cell carcinoma (OSCC) is an ideal cancer on which to
develop our new multimodal imaging approach as it suffers from poor tumor demarcation and is easy to access
with optical imaging tools. We intend to develop an entirely new class of multimodal nanoparticles (NPs) to serve
as our tumor targeting contrast agents. These new NPs are intended to provide real-time fluorescence image
guidance during tumor resection and Raman multiplexed imaging to identify molecular expression and drug
target availability for effective therapy. These multimodal NPs have the potential to provide physicians with a
molecular map of the tumor with improved sensitivity and specificity not previously achievable with existing single
mode molecular imaging technologies. Ongoing attempts toward developing new contrast agents have faced
major problems in gaining regulatory approval. Our innovative approach utilizes the dyes that are already FDA
approved for the coloring of our foods, drugs and cosmetics. Color is all around us, however, we often take for
granted the sources of the vibrant colors we enjoy in our favorite candy, cosmetics and clothing. After curiously
considering that these “colorful” organic dyes could offer more than just aesthetics, we recently discovered that
they in fact have a multitude of useful optical properties (e.g. absorbance, fluorescence, Raman scattering) that
make them ideal for imaging applications. We propose to integrate these dyes and their multimodal imaging
capabilities into a nanoparticle construct specially designed to provide useful imaging contrast that enables
improved cancer detection, localization and molecular profiling. We will begin our study by characterizing the
physical characteristics of these newly fabricated NPs and their multimodal imaging capabilities. This will include
in-vivo evaluation of their biodistribution and extravasation properties by utilizing multiple molecular imaging
tools. We will then test their tumor targeting efficiency in cell culture and on human tissue. Our nanoparticles will
actively target tumors through chemically conjugated targeting ligands and/or passively target the tumor through
the enhanced permeability and retention effect. We will assess the tumor targeting efficiency and surgical
navigation potential of our newly developed NPs with pre-existing preclinical and clinical molecular imaging tools.
These studies will enable the repurposing of these aesthetically pleasing household organic dyes as multimodal
imaging probes to enable an entirely new, and clinically translatable, paradigm. The images generated from
these multimodal nanoparticles could improve cancer detection and localization for improved surgical resection,
but also aid clinicians in the design of treatment protocols which are most suitable for the individual patient.
