Multifunctional nanotubes for in vivo detecting/purging circulating cancer cells

摘要 近年来，前所未有的纳米技术进步有望彻底改变许多领域， 医学和生物学，包括癌症诊断和治疗。大约90%的癌症死亡发生在 从原发肿瘤的转移扩散。循环肿瘤细胞（CTC）计数可能是一个标志物， 转移发展，癌症复发和治疗效果，可用于定制治疗， 来提高癌症患者的存活率。然而，这可能被认为是为时已晚，以治疗病人，因此， 不可能提高他们的生存时，无法治愈的转移已经发展的时候，最初的 诊断与现有的检测。本研究的目的是开发一种新型的多功能无毒金 碳纳米管（GNT）作为超对比剂用于体内实时光声（PA）检测CTCs， 与其光热（PT）治疗相结合。我们将通过以下具体目标来实现这一目标。 目标1。开发先进的多功能混合纳米颗粒，并评估其 体外单细胞水平的癌症综合诊断和治疗。目标2.估计 用于体内检测和治疗标记的模拟CTC的集成PT/PA技术的能力 在动物模型中进行了实验。目标3.确定GNT作为PT/PA造影剂的能力， 在肿瘤发展的不同阶段进行临床前监测和消除CTC。具体目标 4.确定PA流式细胞术（PAFC）使用新型造影剂进行监测的临床能力 转移性肿瘤患者血液循环中的CTC。 无痛、非侵入性PA技术用于定量检测人类CTC的能力将是 在以下阶段进行评估：（1）单独在体内（对照）和体外评估健康志愿者血液， 掺入癌细胞系;和2）离体评估疾病不同阶段的癌症患者血液; 和3）在体内疾病的不同阶段评估癌症患者血液。在这项研究中，我们 将获得统计学上的重要数据，这些数据将证明这种创新技术是前所未有的， 能够在体外和体内定量检测和处理CTC。对公众健康的好处 实现这一目标的方法扩展到常规监测CTC作为微转移的早期标志物， 发展和癌症患者体内癌症复发，以及评估放射的功效， 激光和化疗。

ABSTRACT 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.