DEVELOPMENT OF A CELL-BASED NANOFORMULATED ANTI-TUMOR THERAPY

基于细胞的纳米制剂抗肿瘤疗法的开发

• 批准号: 7960471
• 负责人: Huanyu Dou
• 金额: $ 22.16万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960471
• 关键词: Animal Model; Area; Biological; Biological Models; Biological Monitoring; Bone Marrow; Brain; Brain Diseases; Brain Neoplasms; Brain region; Cells; Computer Retrieval of Information on Scientific Projects Database; Development; Diagnosis; Disease; Disease Outcome; Disorder by Site; Drug Carriers; Drug Delivery Systems; Drug Formulations; Foundations; Funding; Grant; Healthcare Industry; Human; Image; Immune; Institution; Laboratory Animal Models; Malignant Neoplasms; Malignant neoplasm of brain; Nebraska; Neurodegenerative Disorders; Outcome; Pathology; Penetrance; Pharmaceutical Preparations; Physiological; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Site; Source; Structure; Surface; Testing; Therapeutic; Tumor Biology; United States National Institutes of Health; base; chemokine; chemotherapy; design; human disease; improved; infancy; macrophage; monocyte; nanoformulation; nanomedicine; neoplastic; neurotoxicity; particle; response; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of Cell-based drug delivery systems that target disease sites may revolutionize the health care industry. Such cell-based-drug-formulations are in their infancy but have shown "proof of concept". Drugs that are absorbed onto a particle surface and entrapped inside a cell can be dissolved within a particle matrix. Cell-based nanoformulated drug delivery system like those developed herein may be used for treatments and diagnosis of a broad range of diseases including cancer and neurodegenerative disorders. The proposal will develop nanoformulations that can be packaged into macrophages and be delivered to brain tumor sites in laboratory and animal models of human disease. The basis of our drug delivery system is bone marrow or monocyte-derived macrophages (BMM and MDM). These cells will be used as drug carriers. As neuroinflammatory responses are induced by brain tumors including the development of a chemokine gradient, this biological response leads to monocyte-macrophage attraction to diseased brain regions. We posit that BMM or MDM recruited into areas of brain disease can improve therapeutic outcomes by enhancing brain penetrance and/or efficacy. Importantly, our cell-based delivery can improve misdistribution and reduce chemotherapy-induced neurotoxicity. The foundation on which this project is built are recently developed animal model systems that monitor the biologic, immune and physiologic effects of primary human brain tumors. We will utilize an infrastructure of our Nebraska Center for Nanomedicine (NCN) to develop integrated imaging, pathology, and tumor biology platforms to investigate how anti-tumor therapies delivered in cells may be optimally utilized in treatments for malignant brain tumors. The project is designed to test divergent nanoformulations in both laboratory and animal model studies and takes full advantage of the core structures within the NCN. All together, the studies should permit a better understanding of how anti-neoplastic drugs can be effectively most effectively to improve disease outcomes.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 针对疾病部位的基于细胞的药物输送系统的使用可能会给医疗保健行业带来革命性的变化。这种以细胞为基础的药物配方尚处于初级阶段，但已显示出“概念证明”。被吸附在颗粒表面并被包裹在细胞内的药物可以在颗粒基质中溶解。像这里开发的那些基于细胞的纳米配方药物输送系统可用于包括癌症和神经退行性疾病在内的广泛疾病的治疗和诊断。该提案将开发可以包装成巨噬细胞的纳米制剂，并将其输送到实验室和人类疾病动物模型的脑瘤部位。我们的药物输送系统的基础是骨髓或单核细胞来源的巨噬细胞(BMM和MDM)。这些细胞将被用作药物载体。由于神经炎性反应是由脑肿瘤诱导的，包括趋化因子梯度的发展，这种生物学反应导致单核细胞-巨噬细胞吸引到病变的脑区。我们假设，招募到脑部疾病区域的BMM或MDM可以通过增强大脑外显率和/或疗效来改善治疗结果。重要的是，我们的细胞递送可以改善分布不均，减少化疗引起的神经毒性。该项目的基础是最近开发的动物模型系统，该系统可以监测原发人类脑肿瘤的生物、免疫和生理效应。我们将利用内布拉斯加州纳米医学中心(NCN)的基础设施，开发集成的成像、病理学和肿瘤生物学平台，以研究如何将细胞内交付的抗肿瘤疗法最佳地用于恶性脑瘤的治疗。该项目的目的是在实验室和动物模型研究中测试不同的纳米配方，并充分利用NCN内的核心结构。总之，这些研究应该能够更好地理解抗肿瘤药物如何才能最有效地改善疾病结果。