BACE1 Aptamer-Modified Tetrahedral Framework Nucleic Acid to Treat Alzheimer’s Disease in an APP-PS1 Animal Model

Abstract

Alzheimer’s disease is a neurodegenerative disease caused by excessive amyloid β protein-induced neurotoxicity. However, drugs targeting amyloid β protein production face many problems, such as the low utilization rate of drugs by cells and the difficulty of drugs in penetrating the blood–brain barrier. A tetrahedral framework nucleic acid is a new type of nanonucleic acid structure that functions as a therapy and drug carrier. Here, we synthesized a BACE1 aptamer-modified tetrahedral framework nucleic acid and tested its therapeutic effect on Alzheimer’s disease in vitro and in vivo. Our results demonstrated that the tetrahedral framework nucleic acid could be used as a carrier to deliver the BACE1 aptamer to the brain to reduce the production of amyloid β proteins. It also played an antiapoptotic role by reducing the production of reactive oxygen species. Thus, this nanomaterial is a potential drug for Alzheimer’s disease.

Enhanced Nose-to-Brain Delivery of Combined Small Interfering RNAs Using Lesion-Recognizing Nanoparticles for the Synergistic Therapy of Alzheimer’s Disease

“…2-Cyanoprop-2-yl-dithiobenzoate (36 mg), DMAEMA (1.0 g), and AIBN (6.0 mg) were dissolved in methanol and synthesized as described in our previous study. 36 The obtained products were characterized by 1 H NMR spectroscopy (Bruker 600 MHz, CDCl 3 , δ ppm). Gel permeation chromatography (GPC) was performed to measure the weight-average molecular weight.…”

“…To synthesize the ROS-responsive BAP and non-ROS-responsive BB-PDMAEMA (BBP) polymer, PDMAEMA polymers with different DPs were reacted with 4-(bromomethyl)phenylboronic acid and benzyl bromide in DMF at room temperature for 24 h, respectively. After dialysis against deionized water, the obtained products were characterized by 1 H NMR spectroscopy (Bruker 600 MHz, CD 3 OD, δ ppm).…”

Uptake and stability of DNA nanostructures in cells: a cross-sectional overview of the current state of the art

“…10,11 In another example of this material's versatility, RNA-targeting protein RNAse A bound to DNA platforms via sulfo-SMCC protein-DNA chemistry was able to induce cell death in cancer MCF-7 cells. 12 Optimizing the display of ligands, [13][14][15][16] aptamers, [17][18][19] and antigens 20,21 on the NS surface to match the spatial pattern of membrane receptors improves the therapeutic efficacy, particularly the B-cell recognition, of engineered DNA NS as vaccines, 19,20 cancer treatment, or immunogenic treatments. In addition to interfacing with cells, DNA NS can potentially be programmed to remain inactive until the right biological signal stimulates a mechanochemical actuation; these cues can include that originating from light-induced antigen binding, 22 aptamer-protein binding, 9,23 antigen-ligand binding, 24 and many others that are yet to be incorporated into prototypical biomedical systems.…”

Tetrahedral Framework Nucleic Acids Promote Senile Osteoporotic Fracture Repair by Enhancing Osteogenesis and Angiogenesis of Callus

“…Recently, tetrahedral framework nucleic acids (tFNAs), a multifunctional nanoarchitecture assembled by DNA single strands, have attracted ever-increasing attention in the biomedical field . Benefiting from the splendid biocompatibility and editability, tFNAs have been applied in the research of various diseases, including tumor, diabetes, and Alzheimer’s disease . In addition to acting as a carrier, tFNAs themselves also have many biomedical functions, such as promoting osteogenesis, − angiogenesis, − neural regeneration, and wound healing .…”

“…14 Benefiting from the splendid biocompatibility and editability, tFNAs have been applied in the research of various diseases, including tumor, 15 diabetes, 16 and Alzheimer's disease. 17 In addition to acting as a carrier, 18 tFNAs themselves also have many biomedical functions, such as promoting osteogenesis, 19−21 angiogenesis, 22−24 and wound healing. 26 However, the effect of tFNAs on senile osteoporotic fracture repair has not yet been investigated.…”