This proposal aims 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 the 6th most common malignancy, with relatively high mortality rates. The first line of treatment is surgery which suffers from poor tumor margin delineation, resulting in lengthy surgeries and repeat visits. Providing physicians with imaging tools to help detect oral cancers with better sensitivity and specificity has the potential to significantly improve patient outcome. Our innovative approach overcomes regulatory barriers, for faster clinical translation, by using the colorful organic dyes and pigments that we encounter every day. We recently discovered that these materials have a multitude of useful optical properties (e.g. fluorescence, Raman scattering) that make them ideal for tumor imaging. We propose to utilize these untapped properties and incorporate these agents into nano-based imaging contrast agents. We will begin our study with a panel of FDA approved dyes used for coloring food, drugs and cosmetics. As several liposomal drugs have already gained FDA approval, incorporation of these dyes within liposomes eliminates some regulatory hurdles for clinical translation. After fabrication and characterization of our newly developed multimodal liposomes, we will test their tumor targeting efficiency in cell culture and on de-identified human tissue. Our nanoparticles will actively target OSCC tumors through chemically conjugated targeting ligands. We will assess the tumor targeting efficiency and surgical navigation potential of our newly developed nanoparticles with pre-existing molecular imaging tools. It is the hope of this proposed project to evaluate our new molecular imaging strategy first on oral cancer and then apply it to other disease types to improve overall treatment response and patient outcome.