Targeted imaging of brain tumors with a framework nucleic acid probe
Targeted imaging of brain tumors with a framework nucleic acid probe
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使用框架核酸探针对脑肿瘤进行靶向成像
DOI：
10.1021/acsami.7b17927
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发表时间：
2018
影响因子：
9.5
通讯作者：
Fan Chunhai
中科院分区：
文献类型：
--
作者：
Tian Tian;Li Jiang;Xie Cao;Sun Yanhong;Lei Haozhi;Liu Xinyi;Xia Jiaoyun;Shi Jiye;Wang Lihua;Lu Weiyue;Fan Chunhai
开发用于递送药物和成像探针穿过血脑屏障（BBB）的试剂仍然是一个主要挑战。在这项研究中，我们设计了一个生物相容性框架核酸（FNA）为基础的成像探针脑肿瘤靶向。我们采用了一种典型的FNAs，四面体DNA纳米结构（TDNs），作为积木，这是修饰与血管肽-2（ANG），一个19-mer肽来源于人类的抑肽酶Kunitz结构域。该探针与血脑屏障和脑胶质瘤的低密度脂蛋白受体相关蛋白1（LRP-1）具有很高的结合效率。我们发现ANG功能化的TDNs（ANG-TDNs）在血清中保持完整至少12 h，ANG修饰有效地增强了脑毛细血管内皮细胞和乌普萨拉87恶性胶质瘤（U87 MG）细胞对TDNs的细胞摄取。值得注意的是，在体外和体内模型中的研究揭示了ANG-TDNs可以穿过BBB。特别是，在体内成像显示在裸鼠中的U87 MG人胶质母细胞瘤异种移植物中的强荧光信号。这项研究表明，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诊断工具。
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.