PROJECT SUMMARY
Head and neck squamous cell carcinoma (HNSCC), particularly the oral cavity cancer (OrCa) is a debilitating
disease with no increase in overall survival rate for the past decade and the patients undergo significant physical
and psychological toll due to function loss of key organs in the region and cosmetic appearance. Currently the
frontline treatment is surgery, where >5-12 mm of normal tissue region beyond tumor margins are resected to
achieve clear margins and reduce loco-regional recurrence. Adjuvant radiotherapy and chemotherapy are
administered based on the tumor stage, however these therapies had severe toxicity and provided no added
benefit. Overall, there is a dire need for spatially localized therapeutic tools that can aid in tumor eradication
entirely or reduce the tumor burden sufficiently for optimal surgical resection with reduced normal tissue removal.
Photodynamic Therapy (PDT) is an effective, spatially localized cancer treatment with minimal damage to healthy
tissues. Despite its low-cost, success in reducing tumor burden, and excellent healing post-treatment of the oral
mucosa, PDT has yet to become a mainstream frontline therapy primarily because PDT efficacy in solid tumors
depends on significant accumulation of the photosensitizer (PS) at the tumor site, availability of oxygen near the
PS, and effective dosing of the PS-light irradiation combination. Our new nano-platform, Verosite, enhances all
three of these parameters, in addition to aiding image-guided surgery, poising it to significantly improve HNSCC
patient outcomes. Verosite (Verteporfin, Oxygen and Sensing Targeted platform) is a perfluorocarbon (PFC)
based nanoplatform that contains Indocyanine green (ICG) dye for photoacoustic (PAI) and fluorescence (FLI)
imaging contrast, PS verteporfin and oxygen for effective PDT, and will be targeted to Epidermal Growth Factor
Receptor (EGFR), a cell surface biomarker significantly overexpressed in OrCa. Once specifically accumulated
at the tumor, absorption of light by ICG will trigger a liquid to gas phase change of the PFC serves the purpose
to spatio-temporally deliver PS and O2 for effective PDT. Motivated by our promising preliminary data, we
hypothesize that best treatment outcomes (reduced tumor burden, low recurrence and enhanced quality of life
with minimal loss of normal tissue and function) will be obtained with Verosite enabled image-guided surgery
and oxygen enhanced PDT. We evaluate the hypothesis in three specific aims: Aim-1: Synthesize, optimize,
and characterize the Verosite platform, Aim-2: Establish Verosite NDs biodistribution, pharmacokinetics and
dose requirements for PDT in orthotopic OrCa murine models with varying EGFR expression and Aim-3:
Demonstrate that Verosite enabled oxygen enhanced PDT and fluorescence image-guided surgery will aid in
minimal normal tissue resection and enhance survival in various orthotopic OrCa models. Overall, our
customizable multi-functional Verosite platform will enhance PDT efficacy and can be adapted to alleviate
hypoxia in many oxygen-dependent therapies for a broad array of solid tumors.
