Theranostic Nano-objects: Basic Principles and Initial Applications

描述(申请人提供)：我们的目标是为治疗(治疗+诊断)纳米对象的广泛应用建立基础科学基础和工程原理，纳米对象定义为紧凑的自主分子设备，能够在发出有病理事件的信号之前或在采取纠正措施之前分析多个生物标志物。我们的努力将集中在控制动态“neggs”(纳米蛋)行为的方法上，这种动态“neggs”由脱氧核糖核酸组成，包括传感器、成像和/或治疗部分，以及分子计算功能。核蛋可以在提示下打开(解锁)或关闭(锁定)，并且该提示可以是关于一个或多个生物标志物存在或不存在的综合信息。为了展示医用纳米物体的变革潜力，我们将把越来越复杂的奈格斯工程行为映射到其他现有技术都不能令人满意的治疗应用的概念验证。例如，我们将：(I)如果分析物高于(例如葡萄糖)或低于其“正常”浓度(例如加压素)，则打开Negg；(Ii)基于多个表面标记消除/成像狭窄的细胞亚群的标记，同时保护在单一标记上不同的细胞(例如，在淋巴细胞上)；以及(Iii)展示MRI造影剂对目标细胞类型(以b细胞为例)的放大。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