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年: 10.269
【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
【年，卷(期)：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.