A DNA Nanostructure-Based Neuroprotectant against Neuronal Apoptosis via Inhibiting Toll-like Receptor 2 Signaling Pathway in Acute Ischemic Stroke

Abstract

Ischemic stroke is a main cause of cognitive neurological deficits and disability worldwide due to a plethora of neuronal apoptosis. Unfortunately, numerous neuroprotectants for neurons have failed because of biological toxicity, severe side effects, and poor efficacy. Tetrahedral framework nucleic acids (tFNAs) possess excellent biocompatibility and various biological functions. Here, we tested the efficacy of a tFNA for providing neuroprotection against neuronal apoptosis in ischemic stroke. The tFNA prevented apoptosis of neurons (SHSY-5Y cells) caused by oxygen-glucose deprivation/reoxygenation through interfering with ischemia cascades (excitotoxicity and oxidative stress) in vitro. It effectively ameliorated the microenvironment of the ischemic hemisphere by upregulating expression of erythropoietin and inhibiting inflammation, which reversed neuronal loss, alleviated cell apoptosis, significantly shrank the infarction volume from 33.9% to 2.7%, and attenuated neurological deficits in transient middle cerebral artery occlusion (tMCAo) rat models in vivo. In addition, blocking the TLR2-MyD88-NF-κB signaling pathway is a potential mechanism of the neuroprotection by tFNA in ischemic stroke. These findings indicate that tFNA is a safe pleiotropic nanoneuroprotectant and a promising therapeutic strategy for ischemic stroke.

Smart Drug Delivery Systems Based on DNA Nanotechnology

“…In recent years, Lin′s research group has designed a series of tetrahedral frame nucleic acids (tFNA)‐based DNA nanostructures for treatment of different diseases, including new‐onset type 1 diabetes, [109] acute gouty arthritis, [110] intracranial hemorrhage, [111] demyelinating diseases, [112] and so on, achieving remarkably therapeutic effects [113] . Notably, they found tFNA has the intrinsic ability to prevent neuronal apoptosis via blocking the TLR2‐MyD88‐NF‐κB signaling pathway, which could efficiently alleviate the acute ischemic stroke [114] …”

“…[113] Notably, they found tFNA has the intrinsic ability to prevent neuronal apoptosis via blocking the TLR2-MyD88-NF-kB signaling pathway, which could efficiently alleviate the acute ischemic stroke. [114] DNA nanostructures have also been engineered to treat kidney injury. Cai and coworkers reported that DNA origamis preferentially accumulated in the kidneys and showed renalprotective properties in mice with rhabdomyolysis-induced acute kidney injury (AKI) similar to the typical therapeutic drug (N-acetylcysteine).…”

MiR‐26a‐tetrahedral framework nucleic acids mediated osteogenesis of adipose‐derived mesenchymal stem cells

“…Compared with other nanocarriers, tFNAs has good biocompatibility, biodegradability, and biosafety 23,24 . Compared with single‐strand DNA, which needs the assistance of other carriers to enter the cell, tFNAs can enter the cell through the formed three‐dimensional structure, and it can achieve lysosomal escape and targeted localization by connecting specific nucleic acid sequences 25–27 . In recent years, an increasing number of researchers have applied tFNAs to tissue regeneration engineering to explore its multiple effects on cell biological behavior.…”

“… 23 , 24 Compared with single‐strand DNA, which needs the assistance of other carriers to enter the cell, tFNAs can enter the cell through the formed three‐dimensional structure, and it can achieve lysosomal escape and targeted localization by connecting specific nucleic acid sequences. 25 , 26 , 27 In recent years, an increasing number of researchers have applied tFNAs to tissue regeneration engineering to explore its multiple effects on cell biological behavior. It has been found that tFNAs has certain effects on cell proliferation, differentiation, migration, apoptosis, and other biological processes.…”

Development of Nanomaterials to Target Articular Cartilage for Osteoarthritis Therapy

“…Plenty of evidence shows that nanomaterials could be therapeutic molecules combining with targeted tissue directly and be drug delivery systems (DDSs) transporting the drug molecules specifically ( Brown et al, 2019 ; Ummarino et al, 2020 ). In addition, previous studies have demonstrated that nanomaterials have multiple bio-functions ( Zhang et al, 2021 ) [anti-tumor ( Ma et al, 2022 ), anti-inflammation ( Wang et al, 2022 ; Zhang et al, 2022 ), differentiation promotion ( Li S et al, 2021 ), immune modulation ( Qin et al, 2022 ), and neuro-protection ( Zhou et al, 2021 ; Zhu et al, 2022 )]…”