Chemoaffinity Agents For Capturing Prostate Cancer Cells

用于捕获前列腺癌细胞的化学亲和剂

• 批准号: 7666023
• 负责人: Clifford Berkman
• 金额: $ 16.26万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666023
• 关键词: Address; Affinity; Antibodies; Attention; Avidin; Be++ element; Beryllium; Binding; Biological Assay; Biological Markers; Biosensing Techniques; Biotin; Blood; Blood specimen; Cancer Detection; Cell Culture Techniques; Cell Line; Cell Surface Receptors; Cell surface; Cells; Chemicals; Chemistry; Cleaved cell; Core Facility; Detection; Development; Disease; Disseminated Malignant Neoplasm; Dyes; Elements; Endothelium; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Flow Cytometry; Fluorescence Microscopy; Fluorescent Probes; Glutamate Carboxypeptidase II; Goals; Image; Incubated; LNCaP; Label; Malignant Neoplasms; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Methodology; Microscope; Modality; Modeling; Molecular; Monitor; Outcome; PC3 cell line; Patients; Polyethylene Glycols; Prostatic; Quantum Dots; Reagent; Reporter; Research; Risk; Scheme; Site; Slide; Solid; Staging; Streptavidin; Structure; Structure of base of prostate; Technology; Testing; Therapeutic; Therapeutic Agents; Translating; Universities; Washington; Work; anticancer research; base; cancer cell; cancer imaging; clinically relevant; cost; experience; high throughput technology; in vivo; inhibitor/antagonist; innovation; magnetic beads; member; nanoparticle; neovasculature; novel; novel diagnostics; pyrrolidin-3-yl-methanesulfonic acid; research study; scaffold; small molecule; success; targeted delivery; technology development; Address; Affinity; Antibodies; Attention; Avidin; Be++ element; Beryllium; Binding; Biological Assay; Biological Markers; Biosensing Techniques; Biotin; Blood; Blood specimen; Cancer Detection; Cell Culture Techniques; Cell Line; Cell Surface Receptors; Cell surface; Cells; Chemicals; Chemistry; Cleaved cell; Core Facility; Detection; Development; Disease; Disseminated Malignant Neoplasm; Dyes; Elements; Endothelium; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Flow Cytometry; Fluorescence Microscopy; Fluorescent Probes; Glutamate Carboxypeptidase II; Goals; Image; Incubated; LNCaP; Label; Malignant Neoplasms; Malignant neoplasm of prostate; Metastatic Prostate Cancer; Methodology; Microscope; Modality; Modeling; Molecular; Monitor; Outcome; PC3 cell line; Patients; Polyethylene Glycols; Prostatic; Quantum Dots; Reagent; Reporter; Research; Risk; Scheme; Site; Slide; Solid; Staging; Streptavidin; Structure; Structure of base of prostate; Technology; Testing; Therapeutic; Therapeutic Agents; Translating; Universities; Washington; Work; anticancer research; base; cancer cell; cancer imaging; clinically relevant; cost; experience; high throughput technology; in vivo; inhibitor/antagonist; innovation; magnetic beads; member; nanoparticle; neovasculature; novel; novel diagnostics; pyrrolidin-3-yl-methanesulfonic acid; research study; scaffold; small molecule; success; targeted delivery; technology development

DESCRIPTION (provided by applicant): The inhibition of prostate-specific membrane antigen (PSMA) by tight-binding small-molecule inhibitors has not been fully exploited for cell-capture and detection strategies. Our long-term goal is to develop a novel high-throughput technology to capture, image, and quantify metastatic cells that capitalizes on the potency and specific affinity of tight-binding inhibitors for cell-surface hydrolytic enzymes. The overall objective of this R21 application is to prove the concept that high-affinity irreversible inhibitors of PMSA can be employed to capture prostate cancer cells for detection and quantification. Our central hypothesis for the proposed work is that irreversible small-molecule inhibitors of PSMA tethered to a solid support through a cleavable linker can selectively capture prostate cancer cells that express PSMA for detection and quantification. We plan to test our central hypothesis and accomplish our overall objective of this application by pursuing the following specific aims: (1) develop a cell-capture platform for metastatic prostate cancer based on the structural framework of high-affinity inhibitors of PSMA and (2) develop a nanoparticle fluorescent probe to selectively label prostate cancer cells based on the core structure of high-affinity inhibitors of PSMA. The rationale for undertaking the proposed research is that, once we demonstrate that high-affinity small-molecule inhibitors of PSMA tethered to a solid support can selectively capture PSMA-expressing cells, it will serve as a proof-of-concept for the development of novel diagnostic biosensing technology for metastatic prostate cancer in a subsequent R01 proposal. The expected outcomes of this work will be the development of catch and release platforms based on immobilized inhibitors of PSMA as affinity elements will be developed to capture metastatic cancer cells from blood. Secondly, novel nanoparticle agents for detecting and quantifying selectively captured prostate cancer cells will be developed for fluorescence microscopy and flow cytometry applications. The expected positive impact of these results is that it will ultimately assist clinicians in staging prostate cancer, developing personalized therapy modalities, and monitoring treatment. These accomplishments are important, because this work allow for the development of clinically relevant cell-selecting platforms for the detection and sequestering of metastatic prostate cancer cells.

描述（由申请人提供）：通过紧密结合的小分子抑制剂抑制前列腺特异性膜抗原（PSMA），尚未完全利用用于细胞捕获和检测策略。我们的长期目标是开发一种新型的高通量技术，以捕获，图像和量化转移细胞，以利用紧密结合抑制剂对细胞表面水解酶的效力和特定亲和力。该R21应用的总体目标是证明可以使用PMSA的高亲和力不可逆的抑制剂来捕获前列腺癌细胞进行检测和定量的概念。我们针对拟议的工作的中心假设是，通过可裂解的接头将不可逆的小分子抑制剂束缚在固体支持上，可以选择捕获以检测和定量表达PSMA的前列腺癌细胞。我们计划通过追求以下特定目的来检验我们的中心假设，并实现我们的整体目标：（1）基于PSMA的高亲和力抑制剂的结构框架，开发了一个细胞捕获平台，用于转移性前列腺癌，（2）基于PSMA的核心概率，以选择性地标记为核心癌细胞的核心结构。进行拟议的研究的基本原理是，一旦我们证明了将PSMA的高亲和力小分子抑制剂束缚在稳固的支持上可以选择性地捕获表达PSMA的细胞，它将成为新型诊断生物并发性生物验证技术在随后的R01 Possapers possapers the texastatic Prostate癌症中的开发的概念证明。这项工作的预期结果将是基于固定的PSMA抑制剂的捕获和释放平台的发展，因为将开发出亲和力元素以捕获血液中的转移性癌细胞。其次，将开发用于检测和定量选择性捕获的前列腺癌细胞的新型纳米颗粒剂，以用于荧光显微镜和流式细胞仪的应用。这些结果的预期积极影响是，它将最终协助临床医生进行前列腺癌，发展个性化治疗方式和监测治疗。这些成就很重要，因为这项工作允许开发临床相关的细胞选择平台，以检测和隔离转移性前列腺癌细胞。