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使许多领域发生革命性的变化 医学和生物学，包括癌症诊断和治疗。大约90%的癌症死亡病例发生在 来自原发肿瘤的转移和扩散。循环中的肿瘤细胞(CTC)计数可能是一个标志物 转移发展、癌症复发和治疗效果，可用于量身定制的治疗 以提高癌症患者的存活率。然而，治疗病人可能被认为为时已晚，因此， 不可能提高他们的存活率，因为在最初的时候已经出现了无法治愈的转移 用现有的化验方法进行诊断。本方案的目标是开发一种新型的多功能无毒黄金。 碳纳米管(GNTs)作为用于体内CTCs的实时光声(PA)检测的超对比剂， 与他们的光热(PT)治疗相结合。我们将通过以下具体目标实现这一目标。 目标1.开发先进的多功能杂化纳米颗粒并评估其性能 体外单细胞水平的肿瘤综合诊断与治疗。目标2.估计 PT/PA一体化技术在体内检测和治疗标记模拟CTCs的能力 在动物模型中使用GNTT。目的3.确定GNTS作为PT/PA造影剂的能力 临床前监测和消除肿瘤发展不同阶段的CTCs。特定目标 4.用新型造影剂监测PA流式细胞术(PAFC)的临床能力 转移性肿瘤患者血液循环中的CTCs。 一种无痛、无创的PA技术在人类体内定量检测CTCs的能力将是 评估分以下几个阶段进行：(1)健康志愿者血液在体内(对照)和体外单独和 加入癌细胞株；以及2)评估癌症患者在体外疾病不同阶段的血液； 3)在体内评估不同疾病阶段癌症患者的血液。在这项研究过程中，我们 将获得有统计学意义的数据，这些数据将证明这项创新技术史无前例 在体外和体内定量检测和治疗CTCs的能力。对公众健康的好处 实现这一目标的目标扩展到常规监测CTC作为微转移的早期标志 癌症患者体内的发展和癌症复发，以及评估放射治疗的疗效， 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.