Modulation of In Vivo Tumor Oxygenation via Polymersome-encapsulated Myoglobin

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DESCRIPTION (provided by applicant): Over 250,000 new cases of head and neck cancers (HNCs) and non-small cell lung cancers (NSCLCs) are diagnosed every year in the United States. At the time of diagnosis, 60% of these cases are regionally advanced (stage III and IV). Wide surgical excision is not the immediate therapeutic option for most of these locally advanced solid tumor malignancies. A number of studies have shown that a course of combined chemotherapy and radiotherapy, also known as chemoradiotherapy (CRT), promises superior results over chemotherapy or radiation therapy alone. The ability of radiation to eradicate cancer cells depends critically upon the presence of molecular oxygen, a potent radiosensitizer involved in mediating DNA damage. While low oxygen levels (hypoxia) has been recognized as a cause of treatment failure in solid tumors for more than 50 years, previous attempts to improve tumor oxygenation, including whole-body hyperbaric oxygen and systemic erythropoietin treatments, have had limited success. Vindico NanoBioTechnology, Inc. (Vindico), proposes to develop a novel nanoparticle-based therapeutic adjuvant that improves radiation and chemotherapy of HNCs, NSCLCs, as well as other solid tumor malignancies. The goal of this Phase I SBIR project is to create nanoparticle composites that exhibit the requisite in situ properties for safe and effective in vivo oxygen delivery. In colaboration with researchers from Duke University, these agents will be tested for their ability to modulate in vivo tumor oxygenation. Subsequent Phase II work will generate crucial pre-clinical animal data regarding toxicity and the ability of these novel nanoparticles to augment radiotherapy. PUBLIC HEALTH RELEVANCE: The proposed project aims to utilize nanotechnology to deliver a natural protein that increases tumor oxygen levels. This research will have a major impact on public health by resulting in a novel agent that improves cancer radiation and chemotherapy. The end result wil be increased patient survival and an enhanced standard of care. Significant additional advantages include tremendous cost savings to the health care system, in reduced operating and therapeutic costs, as well as local job creation and economic stimulus.