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.
[1]Chinese Acad Sci, Shanghai Inst Appl Phys, Div Phys Biol, Shanghai 201800, Peoples R China.
[2]Chinese Acad Sci, Shanghai Inst Appl Phys, CAS Key Lab Interfacial Phys & Technol, Bioimaging Ctr, Shanghai 201800, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Biomed Res, Shanghai 201203, Peoples R China.
[4]Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China.
[5]Changsha Univ Sci & Technol, Sch Chem & Biol Engn, Changsha 410004, Hunan, Peoples R China.
[6]UCB Pharma, Slough SL1 14EN, Berks, England.
(8.0+极速模式)