Multifunctional nanotubes for in vivo detecting/purging circulating cancer cells

描述（由申请人提供）：近年来前所未有的纳米技术进步有望彻底改变医学和生物学的许多领域，包括癌症诊断和治疗。大约90%的癌症死亡是由原发肿瘤的转移扩散引起的。循环肿瘤细胞（CTC）计数可能是转移发展，癌症复发和治疗效果的标志物，可用于定制治疗，以提高癌症患者的生存率。然而，可能认为治疗患者为时已晚，因此，当使用现有测定法进行初步诊断时已经发生不可治愈的转移时，不可能改善患者的生存率。本提案的目标是开发一种新型的多功能无毒金碳纳米管（GNT）作为超造影剂，用于CTC的体内实时光声（PA）检测，并结合光热（PT）治疗。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，并评估其在体外单细胞水平上对癌症进行综合诊断和治疗的能力。目标2.在动物模型中评估集成PT/PA技术用于体内检测和治疗GNT标记的模拟CTC的能力。目标3：确定GNT作为PT/PA造影剂用于临床前监测和消除肿瘤发展不同阶段的CTC的能力。具体目标4。确定PA流式细胞术（PAFC）与新型造影剂监测转移性肿瘤患者血液循环中CTC的临床能力。将在以下阶段评估用于定量检测人类中CTC的无痛、非侵入性PA技术的能力：（1）评估健康志愿者血液的体内（对照）和体外单独和掺入癌细胞系;和2）评估癌症患者血液在疾病的不同阶段的离体;和3）评估癌症患者血液在疾病的不同阶段的体内。在本研究的过程中，我们将获得统计学上显著的数据，这些数据将证明这种创新技术在体外和体内定量检测和治疗CTC方面前所未有的能力。实现这一目标对公共卫生的益处扩展到常规监测CTC作为癌症患者体内微转移发展和癌症复发的早期标志物，以及评估放射，激光和化疗的疗效。公共卫生相关性：前所未有的纳米技术进步有望彻底改变医学和生物学的许多领域，包括癌症诊断和治疗。该提案的目标是开发新型无毒纳米颗粒作为体内激光检测和治疗循环肿瘤细胞的超造影剂。实现这一目标对公共卫生的益处扩展到循环细胞的常规监测，作为癌症患者体内微转移发展和癌症复发的早期标志物，以及放射治疗，激光治疗和化疗的疗效评估。

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.