The Development of Clinical Grade, Targeted Magnetic Nanoparticles

临床级靶向磁性纳米颗粒的开发

• 批准号: 7983676
• 负责人: RALPH WEISSLEDER, MD, PHD
• 金额: $ 42.35万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983676
• 关键词: Behavior; Benchmarking; Benign; Binding; Biological; Biological Assay; Biological Markers; Blood; Blood Cells; Blood specimen; Caliber; Cancer Detection; Cancer Patient; Cell Count; Cell Separation; Cells; Chemicals; Chemistry; Clinical; Complex; Decision Making; Detection; Development; Diagnostic; Doctor of Medicine; Enzyme-Linked Immunosorbent Assay; Financial compensation; Fine needle aspiration biopsy; Flow Cytometry; Glioma; Goals; Growth Factor Receptors; Hematopoietic Neoplasms; Housing; Human; Hybrids; Individual; Knowledge; Label; Lateral; Leukocytes; Libraries; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Measurement; Measures; Membrane; Metals; Methods; Microfluidics; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Nanotechnology; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Population; Process; Property; Reading; Relapse; Relaxation; Research; Sampling; Sensitivity and Specificity; Site; Specificity; Staging; Stratification; System; Technology; Testing; Therapeutic; Time; Water; Western Blotting; Whole Blood; base; cancer cell; cancer prevention; cancer therapy; chemical property; ferrite; interest; miniaturize; nanomaterials; nanoparticle; neoplastic cell; next generation; novel; novel diagnostics; particle; peripheral blood; physical property; research study; sensor; surface coating; tool; tumor molecular fingerprint; user-friendly; water solubility

The goal of this project is to develop new diagnostic technology for detection and molecular analysis of cancer cells, especially circulating tumor cells. Our approach will be based on the previously developed DMR (diagnostic magnetic resonance) system that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The system measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. In preliminary study, we have detected a few cancer cells in fine needle aspirates, profiled the expression of cellular markers, and measured the pathway inhibition in small numbers of cancer cells. To further advance the DMR technology for molecular and cellular sensing of CTC, we propose three aims: 1) we will synthesize and further develop a new class of magnetic nanoparticles with high magnetic moments and optimize their chemical, biological properties for CTC labeling; 2) we will implement a new DMR chip that can separate CTC from whole blood, measure multiple cancer markers in parallel, and sense the magnetic moments of individual cancer cells; 3) we will evaluate the clinical utility of the developed system using human samples, particularly detecting cancers outlined in the RFA (e.g. ovarian cancer, pancreatic cancer, glioma). Technology, materials and processes developed and optimized in this project will also be useful for Project 4 (implantable NMR based sensors), Projects 1 and 2 (targeting cancer cell populations) and Project 5 (novel hybrid nanomaterials).

该项目的目标是开发新的诊断技术来检测和分子分析癌细胞，特别是循环肿瘤细胞。我们的方法将基于先前开发的 DMR（诊断磁共振）系统，该系统将微型 NMR 探针与靶向磁性纳米颗粒相结合，用于癌细胞的检测和分子分析。该系统测量生物体内水分子的横向弛豫率 其中感兴趣的靶细胞用磁性纳米颗粒标记的样本。在初步研究中，我们在细针抽吸物中检测到了一些癌细胞，分析了细胞标记物的表达，并测量了少量癌细胞的通路抑制。 为了进一步推进用于CTC分子和细胞传感的DMR技术，我们提出了三个目标：1）我们将合成并进一步开发一类具有高磁矩的新型磁性纳米颗粒，并优化其用于CTC标记的化学、生物特性； 2）我们将实现一种新的DMR芯片，可以从全血中分离CTC，并行测量多种癌症标记物，并感测单个癌细胞的磁矩； 3) 我们将使用人体样本评估所开发系统的临床效用，特别是检测 RFA 中概述的癌症（例如卵巢癌、胰腺癌、神经胶质瘤）。该项目开发和优化的技术、材料和工艺也将适用于项目 4（基于 NMR 的植入式传感器）、项目 1 和 2（针对癌细胞群）以及项目 5（新型混合纳米材料）。