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 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.

Hydrogel-mediated drug delivery for treating stroke

Stroke is a common disease and is the major cause of death and disability.It occurs and generates devastating neurological deficits when cerebral blood vessel is blocked(ischemic stroke,IS)or ruptured(hemorrhagic stroke,HS).Hydrogel,being biodegradable and biocompatible,have shown attractive advantages in stroke therapy as a new biomaterial with desirable mechanical properties and tunability of structure,owing to special ability to load different cargoes for multiple treatment strategies,such as pharmacotherapy based on drug-delivery systems and cell therapy including mesenchymal stem cells(MSCs)and neural progenitor cells(NPCs)for improving functional outcomes.However,a comprehensive review of the functional hydrogel for treatment of stroke is still lacking.Therefore,in this work,the main pathological mechanisms of stroke including IS and HS are comprehensively described.The benefits of hydrogel for stroke treatment are also summarized regarding the natural advantages and the delivery advantages.Simultaneously,the application development of hydrogel for treatment of stroke is highlighted.Finally,the unique considerations and challenges in the design and application of hydrogel is discussed for treatment of stroke and clinical application in the future.