DNA framework signal amplification platform-based high-throughput systemic immune monitoring

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 7, 2024

Abstract Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of cells. However, conventional using flow cytometry faces huge challenges in large-scale sample testing, especially mass health screenings, because time-consuming, technical-sensitive high-cost features. the lack high-performance detection platforms hinders development high-throughput technology. To address this bottleneck, we constructed generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution ligands exponential enrichment tetrahedral framework-structured probe design to achieve high-sensitive diverse cells, including CD4+, CD8+ T-lymphocytes, monocytes (down 1/100 μl). Based advanced platform, present novel immune-cell phenotyping system, DSAP, achieving 30-min one-step without cell washing subset showing comparable accuracy with while significantly reducing time cost. As proof-of-concept, DSAP demonstrates excellent diagnostic immunodeficiency staging 107 HIV patients (AUC > 0.97) within 30 min, which can be applied infection screening. Therefore, initially introduced promising open robust routes point-of-care device development.

Language: Английский

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Modulation of Cerebrospinal Fluid Dysregulation via a SPAK and OSR1 Targeted Framework Nucleic Acid in Hydrocephalus

Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)

Published: Feb. 14, 2024

Abstract Hydrocephalus is one of the most common brain disorders and a life‐long incurable condition. An empirical “one‐size‐fits‐all” approach cerebrospinal fluid (CSF) shunting remains mainstay hydrocephalus treatment effective pharmacotherapy options are currently lacking. Macrophage‐mediated ChP inflammation CSF hypersecretion have recently been identified as significant discovery in pathogenesis hydrocephalus. In this study, pioneering DNA nano‐drug (TSOs) developed by modifying S2 ssDNA S4 with SPAK ASO OSR1 tetrahedral framework nucleic acids (tFNAs) synthesis via one‐pot annealing procedure. This construct can significantly knockdown expression OSR1, along their downstream ion channel proteins epithelial cells, thereby leading to decrease secretion. Moreover, these findings indicate that TSOs effectively inhibit M0 M1 phenotypic switch macrophages MAPK pathways, thus mitigating cytokine storm. vivo post‐hemorrhagic (PHH) models, reduce secretion rates, alleviate inflammation, prevent onset These compelling results highlight potential promising therapeutic option for managing hydrocephalus, applications future.

Language: Английский

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Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids

JACS Au, Journal Year: 2025, Volume and Issue: 5(2), P. 486 - 520

Published: Feb. 10, 2025

Tetrahedral framework nucleic acids (tFNAs) represent a promising advancement in acid nanotechnology due to their unique structural properties, high biocompatibility, and multifaceted biomedical applications. Constructed through one-pot annealing method, four single-stranded DNAs self-assemble into stable, three-dimensional tetrahedral nanostructures with enhanced mechanical robustness physiological stability, resisting enzymatic degradation. Their ability permeate mammalian cells without transfection agents, coupled modifiable surfaces, positions tFNAs as versatile carriers for drug gene delivery systems. The tFNA-based platforms exhibit superior therapeutic efficacy, including antioxidative anti-inflammatory effects, alongside efficient cellular uptake tissue penetration. These features underpin role precision medicine, enabling targeted of diverse agents such synthetic compounds, peptides, acids. Additionally, demonstrate significant potential regenerative immune modulation, antibacterial strategies, oncology. By addressing challenges translational integration, stand poised accelerate the development research clinical applications, fostering novel therapies enhancing outcomes across wide spectrum diseases. This Perspective thoroughly details attributes applications critically evaluates tFNAs' potential, outlining inherent implementation exploring solutions these obstacles.

Language: Английский

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Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation

International Journal of Oral Science, Journal Year: 2022, Volume and Issue: 14(1)

Published: Oct. 31, 2022

Abstract With the emergence of DNA nanotechnology in 1980s, self-assembled nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with use a one-step annealing approach. Benefiting from various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, editable functionality, tFNAs been widely applied biomedical field three-dimensional nanomaterials. Surprisingly, exhibit positive effects on biological behaviors regeneration, which may be used treat inflammatory degenerative diseases. According intended application carrying capacity, could carry functional or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, encapsulation based Watson Crick principle. Additionally, dynamic also potential applications controlled targeted therapies. This review summarized latest progress pure/modified/dynamic demonstrated regenerative medicine applications. These include promoting regeneration bone, cartilage, nerve, skin, vasculature, muscle treating diseases bone defects, neurological disorders, joint-related diseases, periodontitis, immune

Language: Английский

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Treatment effect of DNA framework nucleic acids on diffuse microvascular endothelial cell injury after subarachnoid hemorrhage

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(4)

Published: Feb. 21, 2022

The purpose of this study was to investigate the treatment effect and molecular mechanism tetrahedral framework nucleic acids (tFNAs), novel self-assembled acid nanomaterials, in diffuse BMEC injury after SAH.tFNAs were synthesized from four ssDNAs. effects tFNAs on SAH-induced explored by a cytotoxicity model induced hemin, breakdown product hemoglobin, vitro mouse SAH via internal carotid artery puncture vivo. Cell viability assays, wound healing transwell tube formation assays performed explore cellular function like angiogenesis.In demonstrated that could alleviate hemin-induced injury, promote angiogenesis, inhibit apoptosis hemin model. In vivo using H&E TEM results jointly indicated attenuate damage caused situ, showing restored number BMECs endothelium layer more tight intercellular connectivity. Histological examination animals confirmed study, as exhibited against cerebral microvascular bed.Our suggests potential ameliorating SAH, which laid theoretical foundation for further use these nanomaterials tissue engineering vascularization.

Language: Английский

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Bone tissue engineering based on sustained release of MiR29c-modified framework nucleic acids from an injectable hydrogel

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 487, P. 150706 - 150706

Published: March 25, 2024

Language: Английский

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Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering

Materials Today Bio, Journal Year: 2024, Volume and Issue: 25, P. 101011 - 101011

Published: Feb. 27, 2024

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used because its excellent osteoinductive performance. However, application challenged single function conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk (SF) as biomineralized template, thus enabling it to have angiogenic activity achieving the combination organic inorganic substances. Then, rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying freeze-drying method were prepared. CCK-8 test live/dead cell staining showed biocompatibility CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red (ARS), immunofluorescence, western blotting, qRT-PCR that CS/Sr-SF-HA activated expression related genes proteins, inducing osteogenic differentiation rBMSCs. Moreover, tube formation experiments, scratch detection indicated good activity. Furthermore, vivo studies possesses biocompatibility, vascular activity, well ectopic ability subcutaneous pocket rats. This study indicates construction properties has great potential engineering.

Language: Английский

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Tetrahedral framework nucleic acids for improving wound healing

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 16, 2024

Abstract Wounds are one of the most common health issues, and cost wound care healing has continued to increase over past decade. In recent years, there been growing interest in developing innovative strategies enhance efficacy healing. Tetrahedral framework nucleic acids (tFNAs) have emerged as a promising tool for applications due their unique structural functional properties. Therefore, it is great significance summarize tFNAs This review article provides comprehensive overview potential novel therapeutic approach this review, we discuss possible mechanisms highlight role modulating key processes involved healing, such cell proliferation migration, angiogenesis, tissue regeneration. The targeted delivery controlled release capabilities offer advantages terms localized sustained agents site. addition, latest research progress on systematically introduced. We also biocompatibility biosafety tFNAs, along with future directions research. Finally, current challenges prospects briefly discussed promote wider applications.

Language: Английский

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A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(22), P. 22334 - 22354

Published: Oct. 2, 2023

As a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria key therapeutic target DPN. Resveratrol (RSV) widely proven to guard mitochondria, yet unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) promising carriers due their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs form tFNAs-RSV complexes. achieved enhanced stability, bioavailability, biocompatibility compared with alone. With treatment, reactive oxygen species (ROS) production minimized reductases were activated in an vitro model Besides, respiratory function adenosine triphosphate (ATP) enhanced. also exhibited favorable effects on sensory dysfunction, neurovascular deterioration, demyelination, neuroapoptosis DPN mice. Metabolomics analysis revealed that redox regulation energy metabolism two principal mechanisms impacted during process. Comprehensive inspections indicated inhibited nitrosation oxidation reductase chain. In sum, served as mitochondrial nanoguard (mito-guard), representing viable drilling drug development

Language: Английский

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Transcutaneous Immunotherapy for RNAi: A Cascade‐Responsive Decomposable Nanocomplex Based on Polyphenol‐Mediated Framework Nucleic Acid in Psoriasis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(33)

Published: Oct. 5, 2023

Skin is the first barrier against external threats, and skin immune dysfunction leads to multiple diseases. Psoriasis an inflammatory, chronic, common, immune-related disease that affects more than 125 million people worldwide. RNA interference (RNAi) therapy superior traditional therapies, but rapid degradation poor cell uptake are greatest obstacles its clinical transformation. The transdermal delivery of siRNA controllable assembly/disassembly nanodrug systems can maximize therapeutic effect. Tetrahedral framework nucleic acid (tFNA) undoubtedly best carrier for transport genes due excellent noninvasive effect editability. authors combine acid-responsive tannic (TA), RNase H-responsive sequences, siRNA, tFNA into a novel RNAi drug with assembly disassembly: STT. STT has heightened resistance enzyme, serum, lysosomal degradation, size similar tFNA, enabling easy transport. After administration, specifically silence nuclear factor kappa-B (NF-κB) p65, thereby maintaining stability skin's microenvironment reshaping normal defense. This work demonstrates advantages in potential future treatment skin-related

Language: Английский

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