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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要癌症是全球主要的健康问题，是美国第二大死亡原因。这早期发现癌症对于帮助阻止癌症的传播至关重要。循环肿瘤细胞（CTC）是一个标志癌症的这种侵入性行为。这些细胞从原发性肿瘤中分离出来，分解地下室血管的膜，并迁移到血液或淋巴循环中。他们转移到远处它们适应新的微环境的组织，并最终播种并定植以形成转移。当前的癌症检测技术不够敏感，无法在其最早的阶段检测到癌症。但是，只有在癌症尚未转移时，现有治疗才能有效。因此，存在能够在转移之前早期检测到癌症会提高存活率。最近的研究发现，CTC携带有关原发性肿瘤的信息，并且有潜力癌症诊断和进展的有价值的生物标志物。它们还允许某些分子表征原发性肿瘤的生物学特性。 CTC的分子表征已被证明具有很棒的评估癌症的表型和基因型特征的潜力，而无需进行侵入性活检原发性肿瘤。这允许对癌症的最小侵入性患者监测和反应评估治疗。但是，CTC检测受到血液和现代技术的低浓度而阻碍对于CTC检测，有几个主要缺点，例如低重复性，灵敏度和特异性。这种补充应用的目的是创建一种有效的方法来从血液中捕获CTC 对早期癌症检测的高重复性，灵敏度和特异性的癌症患者样本。这会可以通过制造具有明显的捕获和流动区域的金色涂层的电 - 微流体纯富集设备来实现主通道（Auzoneschip），并使用图案化的介电性力量将细胞从流动区引导到捕获区。捕获和流动区域的这种分离使高流量的负面影响最小速度。聚二甲基硅氧烷（PDMS）电 - 微荧光装置将用15 nm厚的金层覆盖表面用硫化捕获抗体进行了修饰。硫化捕获抗体将通过涂有金色的电 - 微富集设备，以捕获抗体修饰主通道的表面通过利用黄金和硫醇组之间的高亲和力。患者血液中CTC上的表面抗原由于高抗原 - 抗体结合亲和力。这种补充应用的另一个重要目标是促进健康的多样性 - 相关研究。这将通过少数群体培训博士后培训，这将是鼓励更多的少数群体参加生物医学科学研究。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.)
影响因子：
0
作者：
Wang,Hai;He,Xiaoming
通讯作者：
He,Xiaoming

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

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

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy.