Organic Spherical Nucleic Acids for the Transport of a NIR‐II‐Emitting Dye Across the Blood–Brain Barrier

• Published in: Angewandte Chemie International Edition 2020-06, Vol.59 (24), p.9702-9710
• Main Authors: Xiao, Fan, Lin, Lin, Chao, Zhicong, Shao, Chen, Chen, Zhe, Wei, Zixiang, Lu, Jingxiong, Huang, Yishun, Li, Lanqing, Liu, Quan, Liang, Yongye, Tian, Leilei
• Format: Article
• Language: English
• Subjects: Biological Transport; Biomedical materials; Block copolymers; Blood-brain barrier; Blood-Brain Barrier - metabolism; Brain cancer; Brain tumors; Cell Line; Coloring Agents - metabolism; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - metabolism; Fluorescence; fluorescent probes; Glioblastoma; Humans; Image resolution; Infrared Rays; Medical imaging; Molecular Imaging; Nanomaterials; Nanotechnology; Neuroimaging; Nucleic acids; spherical nucleic acids; supramolecular chemistry; Tumors
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202002312

DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNA nanotechnology to transport a NIR‐II‐emitting nanofluorophore across the blood–brain barrier (BBB), facilitating non‐invasive imaging of brain tumors. Specifically, the DNA block copolymer, PS‐b‐DNA, is synthesized through a solid‐phase click reaction. We demonstrate that its self‐assembled structure shows exceptional cluster effects, among which BBB‐crossing is the most notable. Therefore, PS‐b‐DNA is utilized as an amphiphilic matrix to fabricate a NIR‐II nanofluorephore, which is applied in in vivo bioimaging. Accordingly, the NIR‐II fluorescence signal of the DNA‐based nanofluorophore localized at a glioblastoma is 3.8‐fold higher than the NIR‐II fluorescence signal of the PEG‐based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors. A DNA block copolymer is used to produce a NIR‐II‐emitting nanofluorophore that can cross the brain–blood barrier (BBB), enabling non‐invasive fluorescence imaging of brain tumors. The dense DNA layer on the surface of the nanofluorophore encapsulates a NIR‐II‐emitting dye and transports it across the BBB using the receptor‐mediated transcytosis pathway.