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

    2022-12-13   点击:[]

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

    【作者】Wenyan Yu; Cuiping Xuan; Bingbing Liu; Lei Zhou; Na Yin; Enpeng Gong; Zhenzhong Zhang; Yinchao Li; Kaixiang Zhang; Jinjin Shi;

    【期刊名】 Nano Research

    【影响因子】 2022: 10.269

    【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

    【年,卷():页码】2022, DOI: https://doi.org/10.1007/s12274-022-4402-7

    【关键词】 Antisense oligonucleotide, Caspase-3, Blood-brain barrier (BBB) penetration, Anti-apoptosis, Ischemic stroke

    【摘要】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.

    【全文链接】https://doi.org/10.1007/s12274-022-4402-7



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