Theranostic Nano-objects: Basic Principles and Initial Applications

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本的科学基础和工程原理，纳米物体被定义为紧凑的自主分子设备，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）的行为的方法上，这些纳米蛋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。核可以根据提示打开（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的存在或不存在的整合信息。为了展示治疗诊断纳米物体的变革潜力，我们将把越来越复杂的neggs工程行为映射到治疗应用的概念验证中，对于这些应用，没有其他现有技术是令人满意的。例如，我们将：（i）如果分析物升高到高于（例如，葡萄糖）或低于（例如，加压素）其“正常”浓度;（ii）基于多个表面标记物标记用于消除/成像细胞的窄亚群，同时保护在单一标记物上不同的细胞（例如，在淋巴细胞上）;和（iii）证明MRI造影剂在靶细胞类型上的扩增（以b细胞为例）。1

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