Modulation of In Vivo Tumor Oxygenation via Polymersome-encapsulated Myoglobin

通过聚合物囊泡包裹的肌红蛋白调节体内肿瘤氧合

• 批准号: 8199371
• 负责人: Paiman Peter Ghoroghchian
• 金额: $ 29.99万
• 依托单位: VINDICO NANOBIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-27 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199371
• 关键词: Acute; Adjuvant; Aerobic; Affect; Binding; Biodegradation; Blood Circulation Time; Boron; Caliber; Cell Proliferation; Characteristics; Chemistry; Collaborations; Cost Savings; Creatinine clearance measurement; DNA Damage; Development; Diagnosis; Distant; Drug Formulations; Drug Kinetics; Economics; Encapsulated; Equilibrium; Erythropoietin; Excision; Exhibits; Generations; Goals; Growth; Head Cancer; Head and Neck Cancer; Healthcare Systems; Hemoglobin; Human; Hyperbaric Oxygen; Hypertension; Hypoxia; Image; In Situ; Infusion procedures; Injection of therapeutic agent; Kinetics; Laboratories; Lead; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mediating; Metmyoglobin; Microcirculation; Molecular; Monitor; Mus; Myoglobin; Myoglobinuria; Nanotechnology; Neck Cancer; Nitric Oxide; Non-Small-Cell Lung Carcinoma; Occupations; Operative Surgical Procedures; Oxygen; Oxygen measurement, partial pressure, arterial; Particle Size; Patients; Pharmacodynamics; Phase; Polymers; Production; Property; Proteins; Public Health; Radiation; Radiation Oncology; Radiation therapy; Radiation-Sensitizing Agents; Reporter; Research; Research Personnel; Resistance; Rhabdomyolysis; Site; Small Business Innovation Research Grant; Solid Neoplasm; Solutions; Staging; Stimulus; Structure; Suspension substance; Suspensions; System; TNFRSF5 gene; Tail; Testing; Therapeutic; Time; Tissues; Toxic effect; Treatment Failure; Tumor Oxygenation; United States; Universities; Veins; Vesicle; Viscosity; Weight; Work; animal data; base; cancer cell; cancer diagnosis; chemical stability; chemotherapy; cost; hyperthermia treatment; hypoxia inducible factor 1; immunogenicity; improved; in vivo; meetings; nanobiotechnology; nanoparticle; nanoscale; nephrotoxicity; novel; particle; pre-clinical; prevent; professor; response; standard of care; success; tumor; uptake; vasoconstriction

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.

描述（由申请人提供）：美国每年诊断出超过250，000例新的头颈癌（HNC）和非小细胞肺癌（NSCLC）病例。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，联合化疗和放疗（也称为放化疗（CRT））的过程中，承诺上级结果优于化疗或放疗单独。辐射根除癌细胞的能力关键取决于分子氧的存在，分子氧是一种参与介导DNA损伤的有效辐射增敏剂。虽然低氧水平（缺氧）已被认为是50多年来实体瘤治疗失败的原因，但以前改善肿瘤氧合的尝试，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）提出开发一种新型的基于纳米颗粒的治疗性佐剂，其改善HNC、NSCLC以及其他实体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，表现出安全有效的体内氧气输送所需的原位特性。在与杜克大学研究人员的合作中，将测试这些药物调节体内肿瘤氧合的能力。随后的第二阶段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。 公共卫生相关性：拟议的项目旨在利用纳米技术提供一种天然蛋白质，增加肿瘤氧水平。这项研究将对公共卫生产生重大影响，因为它将产生一种改善癌症放疗和化疗的新药物。最终的结果将是增加病人的存活率和提高护理标准。显著的其他优势包括为医疗保健系统节省大量成本，降低运营和治疗成本，以及创造当地就业机会和刺激经济。