Application of Programmable Tetrahedral Framework Nucleic Acid-Based Nanomaterials in Neurological Disorders: Progress and Prospects

Chen, Xingyu; Yu, Xianzhong; Liu, Zhiqiang; Lin, Yunfeng

doi:10.3389/fbioe.2021.782237

Cited by 6 publications

(8 citation statements)

References 90 publications

(99 reference statements)

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“…Furthermore, tFNAs have been reported to be neuroprotective [122], antioxidant [123], and anti-inflammatory agents [124]. Chen et al applied tFNA without the conjugation of therapeutic agents or functional agents to target Alzheimer's disease [125]. While the therapeutic properties of tFNA are not yet fully understood, they reported the inhibition of apoptosis and reduction in amyloid beta proteins in the brain, in addition to the ability to partially pass the blood-brain barrier.…”

Section: Tetrahedral Framework Nucleic Acids As Therapeutic Agentsmentioning

confidence: 99%

Therapeutic Applications of Programmable DNA Nanostructures

Aye

Sato

2022

Micromachines

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Deoxyribonucleic acid (DNA) nanotechnology, a frontier in biomedical engineering, is an emerging field that has enabled the engineering of molecular-scale DNA materials with applications in biomedicine such as bioimaging, biodetection, and drug delivery over the past decades. The programmability of DNA nanostructures allows the precise engineering of DNA nanocarriers with controllable shapes, sizes, surface chemistries, and functions to deliver therapeutic and functional payloads to target cells with higher efficiency and enhanced specificity. Programmability and control over design also allow the creation of dynamic devices, such as DNA nanorobots, that can react to external stimuli and execute programmed tasks. This review focuses on the current findings and progress in the field, mainly on the employment of DNA nanostructures such as DNA origami nanorobots, DNA nanotubes, DNA tetrahedra, DNA boxes, and DNA nanoflowers in the biomedical field for therapeutic purposes. We will also discuss the fate of DNA nanostructures in living cells, the major obstacles to overcome, that is, the stability of DNA nanostructures in biomedical applications, and the opportunities for DNA nanostructure-based drug delivery in the future.

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Section: Tetrahedral Framework Nucleic Acids As Therapeutic Agentsmentioning

confidence: 99%

Therapeutic Applications of Programmable DNA Nanostructures

Aye

Sato

2022

Micromachines

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“…[11][12][13][14] Recent research has demonstrated the wide use of DNA nanostructures as drug delivery systems for brain disease because of their ability to pass the blood-brain barrier (BBB). [15][16][17][18][19][20] These properties indicate that DNA nanocages can potentially be used as drug-delivery systems for neurodegenerative diseases and be more suitable than conventional nanoscale drug carriers. 12,[15][16][17] DNA tetrahedral (TD) nanocages formed by self-assembling four synthetic ssDNA oligonucleotides exhibit remarkable mechanical stiffness, nontoxicity, and resistance to nuclease degradation.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19][20] These properties indicate that DNA nanocages can potentially be used as drug-delivery systems for neurodegenerative diseases and be more suitable than conventional nanoscale drug carriers. 12,[15][16][17] DNA tetrahedral (TD) nanocages formed by self-assembling four synthetic ssDNA oligonucleotides exhibit remarkable mechanical stiffness, nontoxicity, and resistance to nuclease degradation. 21,22 DNA tetrahedron provides enough space for small molecules as a nanocarrier and is a promising candidate in drug delivery and bioimaging platforms.…”

Section: Introductionmentioning

confidence: 99%

“…21,33 Recent research has demonstrated the wide use of DNA tetrahedrons as drugdelivery vehicles to treat brain tumours and neurological disorders. 15,18,24 DNA tetrahedrons with and without Angio-peptide-2 penetrated the BBB and were used in brain tumour imaging agents. 24 D Y Yan et al demonstrated that DNA nanostructure with and without BBB-penetrating peptide can cross the BBB in brain cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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DNA Tetrahedral Nanocages as a Promising Nanocarrier for Dopamine Delivery in Neurological Disorders

Singh,

Kansara,

Mandal

et al. 2023

Preprint

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Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson’s disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA-TD as a carrier for Dopamine in cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate these Dopamine-loaded DNA tetrahedral nanostructures’ cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson’s disease and other neurological disorders.

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“…As a promising nanomaterial with good biocompatibility, many DNA nanostructures, such as peptide nucleic acid, spherical nucleic acid, etc., have been widely used in neuroscience. − But in most cases, these DNA nanostructures are often used as nanocarriers and cannot exert neuromodulatory effects . Tetrahedral framework nucleic acid (TFNA), as the simplest three-dimensional DNA nanostructure, has shown vast application potential, too. − In addition to the easy synthesis and good biocompatibility determined by its DNA composition, previous studies have shown that TFNA exerts active biological roles in neuroprotection and anti-inflammatory. − Moreover, TFNA was reported to activate the PI3K-AKT-mTOR signaling pathway, the critical pathway for synapse formation. , As a result, gaining insights into the potential effects of TFNA on neuroplasticity is greatly anticipated.…”

mentioning

confidence: 99%

Positive Neuroplastic Effect of DNA Framework Nucleic Acids on Neuropsychiatric Diseases

Chen

Cui

Liu

et al. 2022

ACS Materials Lett.

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Depression is the most common psychiatric disease characterized by a persistently depressed mood. In patients with major depression, neuroplastic impairments are often observed. The failure rates of antidepressants exceed 30% due to treatment resistance, severe side effects, or prolonged onset of action. There is an absence of fast-acting antidepressants with good biocompatibility. Tetrahedral framework nucleic acid (TFNA), a novel DNA nanodevice, is expected to have extensive application value. Previously, work has examined the biological effect of TFNA on multiple cells types, and TFNA played active roles in neuroprotective and anti-inflammatory. To explore a new research direction for neuroplasticity and a potential mechanism for depression remedies, we tried to define the effects of TFNA on neuroplasticity. The results in vitro showed that TFNA alleviated cytotoxicity and disinhibited proliferation inhibition induced by corticosterone (CORT). In histological studies and behavioral tests, TFNA reduced synapse loss, improved neuronal atrophy, and increased cell number/vitality, thus resulting in improved depression-like behaviors in CORT-induced mice models in the early stages without a toxic effect. Proteins associated with synapse formation and PI3K-AKT-mTOR pathways were also explored to confirm these findings further. Overall, this work demonstrated the positive neuroplastic and therapeutic potential of TFNA for depression.

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Application of Programmable Tetrahedral Framework Nucleic Acid-Based Nanomaterials in Neurological Disorders: Progress and Prospects

Cited by 6 publications

References 90 publications

Therapeutic Applications of Programmable DNA Nanostructures

Therapeutic Applications of Programmable DNA Nanostructures

DNA Tetrahedral Nanocages as a Promising Nanocarrier for Dopamine Delivery in Neurological Disorders

Positive Neuroplastic Effect of DNA Framework Nucleic Acids on Neuropsychiatric Diseases

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