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

基本信息

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
项目类别：
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

项目摘要

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）：在美国，每年诊断出25万例新的头颈癌病例（HNC）和非小细胞肺癌（NSCLC）。在诊断时，这些病例中有60％是在区域晚期的（III和IV期）。对于大多数这些局部晚期实质性肿瘤恶性肿瘤而言，宽外科切除并不是直接的治疗选择。许多研究表明，合并的化学疗法和放射疗法（也称为化学疗法）的组合疗程有望与仅化学疗法或放射治疗相比。辐射根除癌细胞的能力取决于分子氧的存在，分子氧是参与介导DNA损伤的有效放射增敏剂。虽然低氧水平（缺氧）已被认为是实体瘤的治疗衰竭的原因超过50年，但以前的尝试改善肿瘤氧合（包括全身高压氧和全身性红细胞生成素治疗）的尝试取得了有限的成功。 Vindico Nanobiotechnology，Inc。（Vindico）提议开发一种新型的基于纳米颗粒的治疗佐剂，以改善HNC，NSCLCS以及其他实体瘤恶性肿瘤的放射和化学疗法。该阶段I SBIR项目的目的是创建纳米颗粒复合材料，这些纳米颗粒复合材料表现出必要的原位特性，以安全有效地在体内氧气中。在与杜克大学的研究人员共同作品中，这些试剂将通过调节体内肿瘤氧合的能力进行测试。随后的II期工作将产生有关毒性和这些新型纳米颗粒增强放射疗法的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来提供自然蛋白，从而增加肿瘤氧水平。这项研究将对公共卫生产生重大影响，从而改善癌症放射和化学疗法的新药物。最终结果将增加患者的生存和增强的护理标准。额外的额外优势包括减少运营和治疗成本以及当地创造就业机会和经济刺激的巨大成本。