期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 4, 页码 3414-3420出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b17927
关键词
blood-brain barrier; DNA tetrahedron; angiopep-2; glioma; imaging
资金
- Ministry of Science and Technology of China [2016YFA0201200, 2016YFA0400902]
- National Science Foundation of China [11575278, 21675167, 81690263, 21227804, 21505148, 11405013, 31371015]
- Natural Science Foundation of Shanghai [15ZR1448400]
- Key Research Program of Frontier Sciences [QYZDJ-SSW-SLH031]
- Youth Innovation Promotion Association, CAS
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.
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