Carrier-free programmed spherical nucleic acid for effective ischemic stroke therapy via self-delivery antisense oligonucleotide

Antisense oligonucleotide (ASO) for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment. However, its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization, low blood-brain b...

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Bibliographic Details
Published in:Nano research 2023, Vol.16 (1), p.735-745
Main Authors: Yu, Wenyan, Xuan, Cuiping, Liu, Bingbing, Zhou, Lei, Yin, Na, Gong, Enpeng, Zhang, Zhenzhong, Li, Yinchao, Zhang, Kaixiang, Shi, Jinjin
Format: Article
Language:English
Subjects:
Atomic/Molecular Structure and Spectra
Biomedicine
Biotechnology
Chemistry and Materials Science
Condensed Matter Physics
Materials Science
Nanotechnology
Research Article
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Summary:Antisense oligonucleotide (ASO) for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment. However, its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization, low blood-brain barrier (BBB) penetration, poor stability, and potential toxicity of the carrier. Herein, a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure. By co-encoding caspase-3-ASO and transferrin receptor (TfR) aptamer into circle template, the spherical nucleic acid nanostructure (TD) was obtained via self-assembly. The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability (6.4 times) and satisfactory caspase-3 silence effect (2.3 times) due to the dense DNA packaging in TD. Taken together, our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.
ISSN:1998-0124
1998-0000
DOI:10.1007/s12274-022-4402-7