Modulation of In Vivo Tumor Oxygenation via Polymersome-encapsulated Myoglobin

描述（由申请人提供）：在美国，每年有超过250,000例新发头颈癌（HNCs）和非小细胞肺癌（nsclc）被诊断出来。在诊断时，这些病例中有60%是局部晚期（III期和IV期）。广泛的手术切除并不是大多数局部晚期实体瘤恶性肿瘤的直接治疗选择。许多研究表明，化疗和放疗的联合疗程，也被称为放化疗（CRT），比单独的化疗或放疗有更好的效果。辐射根除癌细胞的能力主要取决于分子氧的存在，分子氧是一种有效的辐射增敏剂，参与介导DNA损伤。虽然低氧水平（缺氧）已被认为是实体瘤治疗失败的原因超过50年，但以前尝试改善肿瘤氧合，包括全身高压氧和全身促红细胞生成素治疗，成功有限。Vindico NanoBioTechnology, Inc. （Vindico）提出开发一种新的基于纳米颗粒的治疗辅助剂，以改善HNCs， nsclc以及其他实体肿瘤恶性肿瘤的放疗和化疗。第一阶段SBIR项目的目标是创造纳米颗粒复合材料，该复合材料具有安全有效的体内氧输送所需的原位特性。与杜克大学的研究人员合作，将测试这些药物调节体内肿瘤氧合的能力。随后的II期工作将产生关于毒性和这些新型纳米颗粒增强放射治疗能力的关键临床前动物数据。

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.