Nanotechnology enabled targeting of p53 deficiency in human cancer

纳米技术能够靶向人类癌症中的 p53 缺陷

• 批准号: 10063652
• 负责人: Xiaoming He
• 金额: $ 4.28万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063652
• 关键词: Affinity; Antibodies; Basement membrane; Behavior; Biological; Biopsy; Blood; Blood Circulation; Blood Vessels; Blood specimen; Cancer Detection; Cancer Patient; Cause of Death; Cells; Detection; Devices; Distant; Genotype; Goals; Gold; Health; Human; Liquid substance; Malignant Neoplasms; Microfluidic Microchips; Minority Groups; Molecular; Morbidity - disease rate; Nanotechnology; Neoplasm Circulating Cells; Neoplasm Metastasis; Patient Monitoring; Patients; Pattern; Phenotype; Postdoctoral Fellow; Primary Neoplasm; Property; Public Health; Research; Science; Screening for cancer; Seeds; Sensitivity and Specificity; Speed; Sulfhydryl Compounds; Surface; Surface Antigens; Survival Rate; TP53 gene; Techniques; Technology; Thick; Tissues; Training; United States; Work; antigen antibody binding; cancer biomarkers; cancer diagnosis; cancer therapy; circulating cancer cell; global health; lymphatic circulation; minimally invasive; mortality; novel; patient response; polydimethylsiloxane; tumor progression

Project Summary/Abstract Cancer is a major global health problem and is the second leading cause of death in the United States. The early detection of cancer is vital to help stop the spread of cancer. Circulating tumor cells (CTCs) are a hallmark of this invasive behavior of cancer. These cells detach from the primary tumor, break down the basement membrane of blood vessels, and migrate into the blood or lymphatic circulation. They translocate to distant tissues where they adapt to the new microenvironment, and eventually seed and colonize to form metastases. Current cancer detection techniques are not sensitive enough to be able to detect cancer at its earliest stage. However, existing treatments could be effective only when cancer has not metastasized yet. Therefore, being able to detect cancer early before metastasis increases survival rates. Recent studies have found that CTCs carry information about the primary tumor and have the potential to be valuable biomarkers for cancer diagnosis and progression. They also allow molecular characterization of certain biological properties of the primary tumor. Molecular characterization of CTCs has proven to have a great potential to assess the phenotypic and genotypic features of a cancer without the need for invasive biopsy of the primary tumor. This allows for minimally invasive patient monitoring and response assessment of cancer treatment. However, CTC detection is hindered by its low concentration in blood and contemporary techniques for CTC detection have had several major drawbacks such as low repeatability, sensitivity, and specificity. The goal of this supplemental application is to create an effective approach to capture CTCs from blood samples of cancer patients with high repeatability, sensitivity, and specificity for early cancer detection. This will be achieved by fabricating a gold-coated electro-micro-fluidic device with distinct capture and flow zones in the main channel (AuZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed. The polydimethylsiloxane (PDMS) electro-micro-fluidic device will be coated with a 15 nm thick gold layer and surface modified with thiolated capturing antibody. Thiolated capturing antibodies will be flown through the gold-coated electro-micro-fluidic device, to modify the surface of the main channel with the capturing antibody by utilizing the high affinity between gold and the thiol group. The surface antigens on CTCs from patient blood will allow them to be captured by antibodies modified on the surface of the device due to the high antigen- antibody binding affinity. Another important goal of this supplement application is to promote diversity in health- related research. This will be achieved by training postdoc from a minority group, who will be exemplary to encourage more minority groups to participate in biomedical science research.

项目总结/摘要 癌症是一个主要的全球健康问题，是美国的第二大死亡原因。的 早期发现癌症对帮助阻止癌症扩散至关重要。循环肿瘤细胞（CTC）是一个标志， 癌症的这种侵袭性行为。这些细胞从原发肿瘤上脱落，破坏基底层 血管膜，并迁移到血液或淋巴循环。它们转移到遥远的 它们在组织中适应新的微环境，并最终播种和定殖以形成转移。 目前的癌症检测技术不够灵敏，无法在癌症的最早阶段检测到癌症。 然而，现有的治疗方法只有在癌症尚未转移时才有效。因此， 能够在转移前早期发现癌症增加存活率。 最近的研究发现，CTC携带关于原发性肿瘤的信息，并且有可能成为肿瘤的靶点。 用于癌症诊断和进展的有价值的生物标志物。它们还允许对某些 原发肿瘤的生物学特性。CTC的分子表征已被证明具有很大的 评估癌症的表型和基因型特征而不需要对肿瘤进行侵入性活检的潜力。 原发性肿瘤这允许对癌症进行微创患者监测和反应评估 治疗然而，由于CTC在血液中的低浓度和现代技术，CTC检测受到阻碍 用于CTC检测的方法具有几个主要缺点，例如低重复性、灵敏度和特异性。 该补充申请的目标是创建一种从血液中捕获CTC的有效方法 癌症患者的样本具有高重复性、灵敏度和特异性，可用于早期癌症检测。这将 可以通过制造涂金的电微流体装置来实现，该装置在微流体通道中具有不同的捕获和流动区。 主通道（AuZonesChip），并使用图案化的介电泳力将细胞从流动区引导到 占领区。捕获区和流动区的这种分离将高流量的负面影响最小化 速度聚二甲基硅氧烷（PDMS）电微流体装置将涂覆有15 nm厚的金层 并用硫醇化捕获抗体进行表面修饰。巯基化的捕获抗体将流过 金包被的电微流体装置，以用捕获抗体修饰主通道的表面 通过利用金和巯基之间的高亲和力。来自患者血液的CTC上的表面抗原 将允许它们被由于高抗原而在装置表面上修饰的抗体捕获- 抗体结合亲和力。这种补充剂应用的另一个重要目标是促进健康的多样性- 相关研究。这将通过从少数群体中培养博士后来实现，他们将成为 鼓励更多少数民族参与生物医学科学研究。

项目成果

Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance.

• DOI: 10.1038/s41467-020-20588-0
• 发表时间: 2021-01-12
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Wang H;Liang Y;Yin Y;Zhang J;Su W;White AM;Bin Jiang;Xu J;Zhang Y;Stewart S;Lu X;He X
• 通讯作者: He X

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells and Tumor.

用于癌症干细胞和肿瘤靶向药物输送的纳米颗粒。

• DOI: 10.1007/978-1-4939-8661-3_6
• 发表时间: 2018
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Wang,Hai;He,Xiaoming
• 通讯作者: He,Xiaoming

Targeted Heating of Mitochondria Greatly Augments Nanoparticle-Mediated Cancer Chemotherapy.

• DOI: 10.1002/adhm.202000181
• 发表时间: 2020-07
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Xu J;Shamul JG;Wang H;Lin J;Agarwal P;Sun M;Lu X;Tkaczuk KHR;He X
• 通讯作者: He X

Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.

• DOI: 10.1021/acsnano.2c05195
• 发表时间: 2022-07-26
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Kwizera, Elyahb A.;Ou, Wenquan;Lee, Sojeong;Stewart, Samantha;Shamul, James G.;Xu, Jiangsheng;Tait, Nancy;Tkaczuk, Katherine H. R.;He, Xiaoming
• 通讯作者: He, Xiaoming

Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery.

• DOI: 10.1021/acsnano.7b00824
• 发表时间: 2017-07-25
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Agarwal P;Wang H;Sun M;Xu J;Zhao S;Liu Z;Gooch KJ;Zhao Y;Lu X;He X
• 通讯作者: He X