Hybrid nanoparticles for capture and detection of circulating tumor cells

用于捕获和检测循环肿瘤细胞的混合纳米颗粒

• 批准号: 8879736
• 负责人: Xiaohua Huang
• 金额: $ 40.54万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-13 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8879736
• 关键词: Address; Affinity; Antibodies; Binding; Blood; Blood Circulation; Blood specimen; Breast; Breast Cancer Cell; Breast Cancer Model; Breast Cancer Patient; Cancer Model; Cancer Patient; Cell Adhesion Molecules; Cell Line; Cell surface; Cells; Clinic; Code; Color; Data Analyses; Data Collection; Detection; Devices; Diagnostic Neoplasm Staging; Early Diagnosis; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Event; Flow Cytometry; Goals; Gold; Heterogeneity; Human; Hybrids; Image; Immunomagnetic Separation; Insulin-Like-Growth Factor I Receptor; Intervention; Lead; Leukocytes; Link; Magnetism; Malignant Neoplasms; Metals; Metastatic breast cancer; Microfluidic Microchips; Microfluidics; Microscopic; Modeling; Molecular; Molecular Profiling; Monitor; Negative Staining; Neoplasm Circulating Cells; Neoplasm Metastasis; Online Systems; Optics; Patients; Performance; Physicians; Population Heterogeneity; Research; Resolution; Sensitivity and Specificity; Series; Shapes; Signal Transduction; Site; Specificity; Spectrum Analysis; Surface; System; Techniques; Technology; Therapeutic; Treatment Protocols; Tumor stage; Whole Blood; antibody conjugate; base; cancer cell; design; improved; iron oxide; malignant breast neoplasm; microchip; miniaturize; nanomaterials; nanoparticle; nanoprobe; neoplastic cell; new technology; novel; operation; outcome forecast; overexpression; personalized cancer therapy; personalized medicine; public health relevance; research study; response; tool

 DESCRIPTION (provided by applicant): The goal of this application is to develop a technology platform for capture, detection, enumeration and molecular profiling of circulating tumor cells (CTCs) in blood based on unique integration of novel nanomaterials, advanced optical spectroscopy and robust microfluidics. Sensitive and reliable CTC assessment can provide a powerful tool in the clinic for early diagnosis of cancer and metastasis, prognosis of cancer patients, assessment of tumor stage, monitoring of therapeutic response and ultimately aiding in optimization of treatment regimens. Although significant progress has been made during the last decade, CTC detection remains difficult because CTCs are rare events and a heterogeneous population. An ideal technique should capture CTCs of subpopulations with high efficiency and detect them with high sensitivity and specificity without complicated operations and extensive human intervention. We recently demonstrated that rare breast cancer cells in whole blood (1-2 cells/mL blood) can be dually captured with magnetic separation and detected on-line with surface enhanced Raman scattering (SERS) spectroscopy using antibody-conjugated Raman-coded oval shape iron oxide-gold (IO-Au) core-shell nanoparticles (NPs), raising exciting possibilities of new avenues for CTC detection and analysis. In this project, we propose to make multicolor oval shape IO- Au SERS NPs to recognize CTCs with different markers directly in whole blood, to capture them simultaneously via magnetic separation and to detect them subsequently on a microfluidic device at single cell resolution with the capability of molecular profiling of surface makers using SERS spectroscopy. Combining immunomagnetic enrichment with high specificity, multiplexed targeting for capture of CTC subpopulations, multicolor SERS detection with high sensitivity and specificity, microfluidics for handling rare tumor cells and magnetic-metal nanoparticles for dual enrichment and detection, the integrated yet simple and efficient platform will allow for reliable and more sensitive CTC detection and analysis in routine blood draws, helping physicians to make rational decisions for best personalized cancer treatment. Using breast cancer as a model, the project will be accomplished through the following specific aims: (1) Develop multicolor IO-Au SERS NPs targeting different CTC surface markers namely epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and insulin-like growth factor 1 receptor (IGF1R); (2) Develop a microchip-based system for on-line magnetic enrichment, SERS detection and molecular profiling of CTCs with multiplexed multicolor IO-Au SERS NPs and (3) Assess the capability of our system for detection and molecular profiling of CTCs in blood samples from metastatic breast cancer patients via comparison with conventional flow cytometry. The proposed research will make a high impact in improving the management of patients with breast cancer and other malignancies.

 描述（由申请人提供）：本申请的目标是开发一种基于新型纳米材料、先进的光谱学和稳健的微流体的独特集成的技术平台，用于血液中循环肿瘤细胞（CTC）的捕获、检测、计数和分子谱分析。灵敏可靠的CTC评估可以为临床提供一个强有力的工具，用于癌症和转移的早期诊断、癌症患者的预后、肿瘤分期的评估、治疗反应的监测以及最终帮助优化治疗方案。尽管在过去十年中已经取得了重大进展，但CTC检测仍然很困难，因为CTC是罕见事件和异质性人群。理想的技术应该是高效捕获亚群的CTC，并以高灵敏度和特异性检测它们，而无需复杂的操作和广泛的人为干预。我们最近证明，全血中的罕见乳腺癌细胞（1-2个细胞/mL血液）可以用磁性分离双重捕获，并使用抗体缀合的拉曼编码的椭圆形氧化铁-金（IO-Au）核-壳纳米颗粒（NP）用表面增强拉曼散射（Sers）光谱在线检测，提高了CTC检测和分析新途径的令人兴奋的可能性。在这个项目中，我们提出了一个椭圆形的IO- Au Sers NPs识别CTC与不同的标记直接在全血中，同时捕获它们通过磁分离和检测它们随后在微流控设备上在单细胞分辨率与表面标记的分子谱使用Sers光谱的能力。结合具有高特异性的免疫磁性富集、用于捕获CTC亚群的多重靶向、具有高灵敏度和特异性的Sers检测、用于处理罕见肿瘤细胞的微流体和用于双重富集和检测的磁性金属纳米颗粒，集成而简单且有效的平台将允许在常规检测中进行可靠且更灵敏的CTC检测和分析。 抽血，帮助医生做出最佳个性化癌症治疗的合理决策。本项目以乳腺癌为模型，通过以下具体目标来完成：（1）开发针对不同CTC表面标志物即上皮细胞粘附分子（EpCAM）、表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER 2）和胰岛素样生长因子1受体（IGF 1 R）的金纳米金表面增强拉曼光谱纳米粒;（2）开发基于微芯片的系统，用于在线磁富集，Sers检测和CTC的分子谱分析，具有多路复用的CuClO-Au Sers NPs和（3）通过与常规流式细胞术比较，评估我们的系统用于检测和分子谱分析来自转移性乳腺癌患者的血液样品中的CTC的能力。这项拟议中的研究将对改善乳腺癌和其他恶性肿瘤患者的管理产生重大影响。

项目成果

Size- and Shape-Controlled Synthesis and Properties of Magnetic-Plasmonic Core-Shell Nanoparticles.

磁性质量核心纳米颗粒的尺寸和形状控制的合成和特性。

• DOI: 10.1021/acs.jpcc.6b00875
• 发表时间: 2016-05-19
• 期刊: The journal of physical chemistry. C, Nanomaterials and interfaces
• 作者: Kwizera EA;Chaffin E;Shen X;Chen J;Zou Q;Wu Z;Gai Z;Bhana S;O'Connor R;Wang L;Adhikari H;Mishra SR;Wang Y;Huang X
• 通讯作者: Huang X

Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection.

• DOI: 10.7150/ntno.18216
• 发表时间: 2017
• 期刊: Nanotheranostics
• 作者: Huang X;O'Connor R;Kwizera EA
• 通讯作者: Kwizera EA

Nanotechnology for enrichment and detection of circulating tumor cells.

• DOI: 10.2217/nnm.15.32
• 发表时间: 2015-07
• 期刊: Nanomedicine (London, England)
• 作者: Bhana S;Wang Y;Huang X
• 通讯作者: Huang X

Synthesis and Properties of Magnetic-Optical Core-Shell Nanoparticles.

• DOI: 10.1039/c7ra01224a
• 发表时间: 2017-03-19
• 期刊: RSC advances
• 影响因子: 3.9
• 作者: Kwizera EA;Chaffin E;Wang Y;Huang X
• 通讯作者: Huang X