Development of agents for delivering drugs and imaging probes across the blood–brain barrier (BBB) remains a major challenge. In this study, we designed a biocompatible framework nucleic acid (FNA)-based imaging probe for brain tumor-targeting. We employed a typical type of FNAs, tetrahedral DNA nanostructures (TDNs), as the building block, which were modified with angiopep-2 (ANG), a 19-mer peptide derived from human Kunitz domain of aprotinin. This probe exhibited high binding efficiency with low-density lipoprotein receptor-related protein-1 (LRP-1) of BBB and glioma. We found that ANG-functionalized TDNs (ANG-TDNs) stayed intact for at least 12 h in serum, and that ANG modification effectively enhanced cellular uptake of TDNs in brain capillary endothelial cells and Uppsala 87 malignant glioma (U87MG) cells. Remarkably, studies in both in vitro and in vivo models revealed that ANG-TDNs could cross the BBB. Especially, in vivo imaging showed strong fluorescent signals in U87MG human glioblastoma xenograft in nude mice. This study establishes that the FNA-based platform provides a new theranostic tool for the study and therapy of brain tumors.

中文翻译：

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用框架核酸探针对脑肿瘤进行靶向成像

跨血脑屏障（BBB）的药物和成像探针的输送剂的开发仍然是一项重大挑战。在这项研究中，我们设计了一种针对脑肿瘤靶向的基于生物相容性框架核酸（FNA）的成像探针。我们采用了典型的FNA类型，即四面体DNA纳米结构（TDN）作为构建基块，并使用angiopep-2（ANG）（一种由人抑肽酶的Kunitz结构域衍生的肽）进行了修饰。该探针显示出与BBB和神经胶质瘤的低密度脂蛋白受体相关蛋白1（LRP-1）的高结合效率。我们发现，ANG官能化的TDNs（ANG-TDNs）在血清中保持完整至少12 h，并且ANG修饰有效地增强了脑毛细血管内皮细胞和Uppsala 87恶性神经胶质瘤（U87MG）细胞中TDNs的细胞摄取。值得注意的是 在体外和体内模型中的研究表明，ANG-TDNs可以穿越血脑屏障。特别是，体内成像在裸鼠的U87MG人胶质母细胞瘤异种移植物中显示出强荧光信号。这项研究建立了基于FNA的平台，为脑肿瘤的研究和治疗提供了一种新的治疗方法。