Theranostic Nano-objects: Basic Principles and Initial Applications

治疗诊断纳米物体：基本原理和初步应用

• 批准号: 8411867
• 负责人: Milan N Stojanovic
• 金额: $ 119.07万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-27 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411867
• 关键词: Address; Affinity; Antibodies; Basic Science; Behavior; Behavior Control; Biological Markers; Boxing; Cancer Patient; Cell surface; Cells; Complex; Contrast Media; Cues; DNA; Development; Devices; Diabetes Mellitus; Diagnostic; Diagnostic Imaging; Drops; Engineering; Enzymes; Event; Fluorescence; Foundations; Generations; Glucose; Goals; Image; Insulin; Intensive Care; Label; Laboratories; Lead; Lymphocyte; Lymphocyte Subset; Magnetic Resonance Imaging; Maps; Medical; Methods; Molecular; Molecular Machines; Movement; Nanotechnology; Outcome; Patients; Prodrugs; Protocols documentation; Shock; Signal Transduction; Solutions; Structure of beta Cell of islet; Surface; Technology; Therapeutic; Toxin; Vasopressins; aptamer; base; cell type; egg; glucose oxidase; in vivo; molecular scale; nano; nanodiagnostic; operation; prevent; response; sensor; tool

DESCRIPTION (provided by applicant): Our goal is to establish basic science foundations and engineering principles for the broad applications of theranostic (therapeutic+diagnostic) nano-objects, defined as compact autonomous molecular devices capable of analyzing multiple biomarkers before signaling that there are pathological events or before taking corrective actions. Our effort will center on methods to control behavior of dynamic "neggs" (nano-eggs), made of deoxyribonucleic acids, and comprising sensors, imaging and/or therapeutic moieties, and molecular computing functions. Neggs can open (be unlocked) or close (be locked) on cue, and this cue can be integrated information on the presence or absence of one or more biomarkers. In order to showcase the transformative potential of theranostic nano-objects, we will map increasingly complex engineered behaviors of neggs to proof-of-concepts for therapeutic applications for which no other existing technologies are satisfactory. For example, we will: (i) open a negg if an analyte raises above (e.g., glucose) or drops below (e.g., vasopressin) its "normal" concentration; (ii) mark for elimination/imaging narrow subpopulations of cells based on multiple surface markers, while protecting cells that differ in a single marker (e.g., on lymphocytes); and (iii) demonstrate amplification of MRI contrast agents on a targeted cell type (exemplified on b-cells). 1 PUBLIC HEALTH RELEVANCE: Theranostic (therapeutic+diagnostic) nano-objects are autonomous nanoscopic devices capable of analyzing in vivo multiple biomarkers before signaling the presence of pathological events (imaging/diagnostics) or before taking corrective actions when needed (therapeutics). They can autonomously control levels of glucose in diabetes, prevent irreversible shock in an intensive care patient, or selectively eliminate very narrow subpopulations of cells in a cancer patient.

描述（由申请人提供）：我们的目标是为治疗诊断（治疗+诊断）纳米物体的广泛应用建立基础科学基础和工程原理，纳米物体被定义为紧凑的自主分子装置，能够在发出病理事件信号或采取纠正措施之前分析多种生物标志物。我们的努力将集中在控制动态“neggs”（纳米蛋）行为的方法上，动态“neggs”由脱氧核糖核酸制成，包括传感器、成像和/或治疗部分以及分子计算功能。 Neggs可以根据提示打开（解锁）或关闭（锁定），并且该提示可以是关于一种或多种生物标志物存在或不存在的综合信息。为了展示治疗诊断纳米物体的变革潜力，我们将把日益复杂的纳米物体工程行为映射到其他现有技术无法令人满意的治疗应用的概念验证。例如，我们将： (i) 如果分析物浓度高于（例如，葡萄糖）或低于（例如，加压素）其“正常”浓度，则打开 negg； (ii) 基于多个表面标记物对狭窄的细胞亚群进行消除/成像标记，同时保护单个标记物不同的细胞（例如，淋巴细胞）； (iii) 证明 MRI 造影剂对目标细胞类型（以 b 细胞为例）的放大作用。 1 公共健康相关性：治疗诊断（治疗+诊断）纳米物体是自主纳米设备，能够在发出病理事件存在信号（成像/诊断）或在需要时采取纠正措施（治疗）之前分析体内多种生物标志物。它们可以自主控制糖尿病患者的血糖水平，防止重症监护患者出现不可逆的休克，或者选择性地消除癌症患者体内非常狭窄的细胞亚群。