Transferrin Aptamers Increase the In Vivo Blood-Brain Barrier Targeting of Protein Spherical Nucleic Acids

被引:11
|
作者
Kusmierz, Caroline D. [1 ,2 ]
Callmann, Cassandra E. [1 ,2 ]
Kudruk, Sergej [1 ,2 ]
Distler, Max E. [1 ,2 ]
Mirkin, Chad A. [1 ,2 ]
机构
[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[2] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA
基金
美国国家卫生研究院;
关键词
CELLULAR UPTAKE; BIFUNCTIONAL APTAMER; RECEPTOR ANTIBODY; DELIVERY; ENDOCYTOSIS; VITRO; NANOPARTICLES; MODEL;
D O I
10.1021/acs.bioconjchem.2c00389
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The systemic delivery of exogenous proteins to cells within the brain and central nervous system (CNS) is challenging due to the selective impermeability of the blood-brain barrier (BBB). Herein, we hypothesized that protein delivery to the brain could be improved via functionalization with DNA aptamers designed to bind transferrin (TfR) receptors present on the endothelial cells that line the BBB. Using g-galactosidase (g-Gal) as a model protein, we synthesized protein spherical nucleic acids (ProSNAs) comprised of g-Gal decorated with TfR aptamers (Transferrin-ProSNAs). The TfR aptamer motif significantly increases the accumulation of g-Gal in brain tissue in vivo following intravenous injection over both the native protein and ProSNAs containing nontargeting DNA sequences. Furthermore, the widespread distribution of g-Gal throughout the brain is only observed for Transferrin-ProSNAs. Together, this work shows that the SNA architecture can be used to selectively deliver protein cargo to the brain and CNS if the appropriate aptamer sequence is employed as the DNA shell. Moreover, this highlights the importance of DNA sequence design and provides a potential new avenue for designing highly targeted protein delivery systems by combining the power of DNA aptamers together with the SNA platform.
引用
收藏
页码:1803 / 1810
页数:8
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