Cancer biomarkers are directly related to the development of cancers. Noninvasive identification of the location and expression levels of these biomarkers in live cancer cells offers great potential for accurate early-stage cancer diagnosis and cancer metastasis monitoring. Herein, we propose a DNA-engineered exosome (DNA-Exo) nanoplatform to image dual cancer biomarkers at the single-cell level, in which DNA probes were modified with the cholesterol group to facilely anchor on the exosomal membrane through hydrophobic interaction. Fluorophore-labeled DNA aptamer and hairpin probes targeting two kinds of cancer biomarkers of transmembrane glycoprotein mucin 1 (MUC1) and cytoplasmic microRNA-21 (miR-21), respectively, were employed for convenient dual-fluorescence imaging of cancer cells. The cellular uptake of DNA-Exos induced the specific recognition of MUC1 and miR-21, allowing the acquisition of the expression levels and spatial distributions of these two biomarkers in three tested cell lines. Our work demonstrated that the proposed DNA-Exos with designable functions have the capacity to visually discriminate different cell types based on the specific recognition of analytes.

中文翻译：

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基于DNA工程外泌体的活细胞中癌症生物标记物的同时成像

癌症生物标志物与癌症的发展直接相关。这些生物标志物在活癌细胞中的位置和表达水平的非侵入性鉴定为准确的早期癌症诊断和癌症转移监测提供了巨大的潜力。在这里，我们提出了一种DNA工程化的外泌体（DNA-Exo）纳米平台，以在单细胞水平上成像双重癌症生物标志物，其中DNA探针被胆固醇基团修饰，可以通过疏水相互作用轻松锚定在外泌体膜上。荧光素标记的DNA适体和发夹探针分别针对跨膜糖蛋白粘蛋白1（MUC1）和细胞质microRNA-21（miR-21）的两种癌症生物标志物，用于方便的癌细胞双荧光成像。DNA-Exos的细胞摄取诱导了对MUC1和miR-21的特异性识别，从而可以在三种测试的细胞系中获得这两种生物标记的表达水平和空间分布。我们的工作表明，所提出的具有可设计功能的DNA-Exos具有基于分析物的特异性识别，在视觉上区分不同细胞类型的能力。