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 

机构地区：[1]School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China [2]Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Zhengzhou 450001,China [3]Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou 450001,China

出　　处：《Nano Research》2023年第1期735-745,共11页纳米研究（英文版）

基　　金：This work was funded by the National Natural Science Foundation of China(Nos.82073395 and 319009919);Postdoctoral Science Foundation of China(Nos.2020TQ0288).

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.

关 键 词：antisense oligonucleotide caspase-3 blood-brain barrier(BBB)penetration ANTI-APOPTOSIS ischemic stroke 

分 类 号：R743.3[医药卫生—神经病学与精神病学]