Multifunctional nanotubes for in vivo detecting/purging circulating cancer cells

用于体内检测/清除循环癌细胞的多功能纳米管

• 批准号: 7892539
• 负责人: Vladimir P Zharov
• 金额: $ 30.29万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7892539
• 关键词: Ablation; Animal Model; Appearance; Area; Atomic Force Microscopy; Biological Assay; Biology; Blood; Blood Circulation; Blood specimen; Cancer Diagnostics; Cancer Patient; Cancer cell line; Carbon Nanotubes; Cell Count; Cells; Cessation of life; Clinical; Clinical Research; Contrast Media; Control Groups; Data; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Early Diagnosis; Flow Cytometry; Goals; Gold; Human; Hybrids; In Vitro; Individual; Injection of therapeutic agent; Label; Lasers; Low-Level Laser Therapy; Magnetism; Malignant Neoplasms; Medicine; Methods; Micrometastasis; Molecular Target; Monitor; Mus; Nanotubes; Neoplasm Metastasis; Painless; Patients; Prevention; Primary Neoplasm; Public Health; Radiation therapy; Recurrence; Research; Signal Transduction; Staging; Techniques; Technology; Testing; Therapeutic; Time; Transmission Electron Microscopy; Treatment Efficacy; Tumor stage; cancer cell; cancer recurrence; cancer therapy; cell injury; chemotherapy; circulating cancer cell; efficacy evaluation; healthy volunteer; improved; in vivo; innovation; malignant breast neoplasm; nanoparticle; neoplastic cell; new technology; novel; pre-clinical; prevent; public health relevance; purge; tumor

DESCRIPTION (provided by applicant): Unprecedented nanotechnological advances in recent years hold the promise of revolutionizing many areas of medicine and biology, including cancer diagnostics and treatment. Approximately 90% of all cancer death arise from the metastasis spread of primary tumor. The circulating tumor cell (CTC) counts may be a marker of metastatic development, cancer recurrence, and therapeutic efficacy, which could be used to tailor therapy in order to improve cancer patient survival. However, it might be considered too late to treat patients and, hence, impossible to improve their survival when incurable metastases have already developed by the time of initial diagnosis with existing assays. The goal of this proposal is to develop a novel multifunctional not-toxic gold carbon nanotubes (GNTs) as super-contrast agent for in vivo real-time photoacoustic (PA) detection of CTCs, integrated with their photothermal (PT) treatment. We will pursue this goal through the following Specific Aims. Aim 1. Develop advanced multifunctional hybrid nanoparticles and assess their capability for integrated diagnosis and therapy of cancer at the single-cell level in vitro. Aim 2. Estimate the capability of the integrated PT/PA technique for in vivo detection and therapy of mimic CTCs labeled with GNTs in an animal model. Aim 3. Ascertain the capability of GNTs as PT/PA contrast agents for preclinical monitoring and elimination of CTCs at different stages of tumor development. Specific Aim 4. Determine the clinical capability of PA flow cytometry (PAFC) with novel contrast agents to monitor CTCs in the blood circulation of patients with metastatic tumors. The capability of a painless, non-invasive, PA technique for quantitative detection of CTCs in humans will be assessed in following stages: (1) assessment of healthy volunteer blood in vivo (control) and in vitro alone and spiked with cancer cell lines; and 2) assessment of cancer patient blood at different stages of disease ex vivo; and 3) assessment of cancer patient blood at different stages of disease in vivo. In the course of this study, we will obtain statistically significant data that will demonstrate this innovative technique's unprecedented capability for quantitatively detection and treatment CTCs in vitro and in vivo. The benefits to the public health of achieving this goal extend to routinely monitoring CTCs as early markers for the micrometastasis development and cancer recurrence in vivo in cancer patients, as well as to evaluating the efficacy of radiation, laser and chemotherapy. PUBLIC HEALTH RELEVANCE: Unprecedented nanotechnological advances hold the promise of revolutionizing many areas of medicine and biology, including cancer diagnostics and treatment. The goal of this proposal is to develop novel nontoxic nanoparticles as supercontrast agents for in vivo laser detection and treatment of circulating tumor cells. The benefits to the public health of achieving this goal extend to the routine monitoring of circulating cells as early markers for micrometastasis development and cancer recurrence in vivo in cancer patients, as well as to the evaluation of the efficacy of radiation therapy, laser therapy, and chemotherapy.

描述（由申请人提供）：近年来，史无前例的纳米技术进步有望彻底改变医学和生物学领域的许多领域，包括癌症的诊断和治疗。所有癌症死亡中约有90％来自原发性肿瘤的转移扩散。循环肿瘤细胞（CTC）计数可能是转移性发育，癌症复发和治疗功效的标志，可用于调整治疗以改善癌症患者的生存。但是，治疗患者的治疗可能为时已晚，因此，当无法治愈的转移已经发展为现有测定时，无法改善其生存率。该提案的目的是开发一种新型的多功能金碳纳米管（GNTS）作为体内实时光声（PA）检测CTC的超对比度，并与光热（PT）进行集成。我们将通过以下特定目标实现这一目标。 AIM 1。发展晚期多功能杂交纳米颗粒，并评估其在体外单细胞水平综合诊断和治疗癌症的能力。目标2。估计综合PT/PA技术在动物模型中标记为GNT的模拟CTC的体内检测和治疗的能力。 AIM 3。确定GNT作为PT/PA对比剂的能力，可在肿瘤发育的不同阶段进行临床前监测和消除CTC。具体目的4。确定具有新型对比剂的PA流式细胞仪（PAFC）的临床能力，以监测转移性肿瘤患者血液循环中的CTC。将在接下来的阶段评估一种无痛的，无创的PA技术来定量对人类CTC进行定量检测的能力：（1）评估体内健康志愿者血液（对照）和单独的体外，并用癌细胞系峰值； 2）评估疾病的不同阶段的癌症患者血液； 3）评估体内疾病不同阶段的癌症患者血液。在这项研究的过程中，我们将获得具有统计学意义的数据，这些数据将证明这种创新技术在体外和体内进行定量检测和治疗CTC的前所未有的能力。实现这一目标的公共卫生的好处扩展到常规监测CTC作为癌症患者体内微量含量发育和癌症复发的早期标记，并评估放射线，激光和化学疗法的疗效。公共卫生相关性：前所未有的纳米技术进步具有彻底改变医学和生物学领域（包括癌症诊断和治疗）的希望。该提案的目的是开发新型的无毒纳米颗粒作为用于体内激光检测和治疗循环肿瘤细胞的超对比剂。实现这一目标的公共卫生的好处扩展到对循环细胞作为癌症患者体内微量表发育和癌症复发的早期标记的常规监测，以及评估放射治疗，激光疗法和化学疗法的功效。