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 MicroRNA Therapeutics: from Preclinical to Clinical Studies

Human Gene Therapy, Journal Year: 2024, Volume and Issue: 35(17-18), P. 628 - 648

Published: Aug. 16, 2024

MicroRNAs (miRNAs) are crucial regulators of gene expression involved in various pathophysiological processes. Their ability to modulate multiple pathways simultaneously and their involvement numerous diseases make miRNAs attractive tools targets therapeutic development. Significant efforts have been made advance miRNA research the preclinical stage, attracting considerable investment from biopharmaceutical companies. Consequently, an increasing number miRNA-based therapies entered clinical trials for both diagnostic applications across a wide range diseases. While individual can regulate broad array mRNA targets, this also complicates management adverse effects seen trials. Several candidates discontinued due toxicity concerns, underscoring need comprehensive risk assessments therapeutics. Despite no strategies yet received approval regulatory agencies, prominent progress modulation approaches nano-delivery systems last decade, leading development novel safe well-tolerated drug candidates. In review, we present recent advances therapeutics currently or stages treating rare genetic disorders multifactorial common conditions. We address challenges related safety targeted delivery therapies, as well identification most effective

Language: Английский

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Programmable Tetrahedral DNA‐RNA Nanocages Woven with Stimuli‐Responsive siRNA for Enhancing Therapeutic Efficacy of Multidrug‐Resistant Tumors

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 25, 2024

Abstract Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli‐responsive programmable tetrahedral DNA‐RNA nanocages (TDRN) have been rationally designed developed for dynamic co‐delivery doxorubicin P‐glycoprotein (P‐gp) siRNA. Specifically, sense antisense strand sequences P‐gp siRNA, which are bricks with terminal disulfide bond conjugation, precisely embedded in one edge DNA tetrahedron. TDRN provides release element control functional cargo that significantly more stable than “tail‐like” TDN nanostructures. highly rigid 3D nanostructure siRNA‐organized demonstrated notable improvement stability RNase A mouse serum, well long‐term storage up 4 weeks, evidenced by this study. These biocompatible multifunctional nanocarriers gold nanocluster‐assisted delivery (TDRN@Dox@AuNC p ) successfully used achieve synergistic RNAi/Chemo‐therapy vitro vivo. This system, integrates RNAi therapy chemotherapy, offers promising approach treating multidrug‐resistant tumors.

Language: Английский

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Effect of tetrahedral framework nucleic acids on the reconstruction of tendon‐to‐bone injuries after rotator cuff tears

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(6)

Published: Jan. 28, 2024

Abstract Clinicians and researchers have always faced challenges in performing surgery for rotator cuff tears (RCT) due to the intricate nature of tendon‐bone gradient limited long‐term effectiveness. At same time, occurrence an inflammatory microenvironment further aggravates tissue damage, which has a negative impact on regeneration process mesenchymal stem cells (MSCs) eventually leads production scar tissue. Tetrahedral framework nucleic acids (tFNAs), novel nanomaterials, shown great potential biomedicine their strong biocompatibility, excellent cellular internalisation ability, unparalleled programmability. The objective this research was examine if tFNAs positive effect after RCTs. Experiments conducted controlled environment demonstrated that hindered assembly inflammasomes macrophages, resulting decrease release factors. Next, were exert protective osteogenic chondrogenic differentiation bone marrow MSCs under conditions. vitro results also regulatory tendon‐related protein expression levels tenocytes stimulation. Finally, intra‐articular injection into rat RCT model showed improved tendon‐to‐bone healing, suggesting may be promising agents treatment

Language: Английский

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A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition

Advanced Science, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 20, 2023

There has been considerable interest in gene vectors and their role regulating cellular activities treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate expression post-transcriptionally treat a range diseases. An original tetrahedral framework (tFNA) analog, bioswitchable miR inhibitor delivery system (BiRDS) carrying inhibitors, is previously established; however, it remains unknown whether BiRDS can be equipped with mimics. Taking advantage transport capacity upgrading further, treatment outcomes traditional tFNA at different concentrations on TGF-β- bleomycin-induced fibrosis simultaneously vitro vivo compared. upgraded designed by successfully synthesizing novel BiRDS, mimic, miR-27a, for skin inhibiting pyroptosis pathway, which exhibits stability biocompatibility. three times higher efficiency delivering miRNAs than conventional sticky ends. Moreover, more potent against pyroptosis-related tFNAs. These findings indicate that applied drug disease treatment.

Language: Английский

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A Noninvasive Nanoeyedrop Therapy for the Inhibition of Uveal Melanoma: Tetrahedral Framework Nucleic Acid–Based Bioswitchable MicroRNA Delivery System

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy, exhibiting pronounced invasive characteristics and a dismal prognosis. Conventional therapeutic modalities, including radiotherapy, laser therapy, surgery, are frequently can lead to complications, underscoring need for development of efficacious, safe, noninvasive approaches. This study investigated tetrahedral framework nucleic acid (tFNA)-based bioswitchable microRNA (miRNA) delivery system, designated BiRDS, engineered inhibition UM through use miRNA suppressors via eyedrops. The BiRDS construct exhibited structure, which was small in size, easily synthesizable, stable, biosafe, able efficiently carry miR-30a-5p into cells. Functionally, observed inhibit proliferation, migration, invasion cells while promoting apoptosis miR-30a-5p/E2F7 axis. It noteworthy that nanoeyedrops were penetrate complex ocular barrier structure reach fundus, thereby inhibiting growth xenograft model. As patient-friendly, eyedrop-based not only inhibited without enucleation eyeball but also expected improve patient compliance quality life providing safer alternative drug administration. work substantiates as potential paradigm shift local treatment early UM, facilitating its application treating other diseases therapies.

Language: Английский

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A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids: Application to endogenous regeneration of articular cartilage

Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 634 - 648

Published: Aug. 19, 2024

Articular cartilage injury (ACI) remains one of the key challenges in regenerative medicine, as current treatment strategies do not result ideal regeneration hyaline-like cartilage. Enhancing endogenous repair via microRNAs (miRNAs) shows promise a therapy. miRNA-140 and miRNA-455 are two promising candidates for regulating chondrogenic differentiation mesenchymal stem cells (MSCs). In this study, we innovatively synthesized multifunctional tetrahedral framework which nucleic acid (tFNA)-based targeting miRNA codelivery system, named A-T-M, was used. With tFNAs vehicles, miR-140 miR-455 were connected to modified on tFNAs, while Apt19S (a DNA aptamer MSCs) directly integrated into nanocomplex. The relevant results showed that A-T-M efficiently delivered MSCs subsequently regulated MSC through corresponding mechanisms. Interestingly, synergistic effect between revealed. Furthermore, successfully enhanced capacity articular vivo effectively inhibited hypertrophic chondrocyte formation. provides new perspective strategy cartilage, showing strong clinical application value future ACI.

Language: Английский

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A Multifunctional Nanocomplex as miRNA/Antibiotic Co‐Delivery System Based on Tetrahedral Framework DNA: Application to Infected Wound Healing

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Abstract Infected wounds are a complex disease involving bacterial infections and dysregulated inflammation. However, current research has mostly focused on inhibition rather than Thus, combined therapeutic strategies with anti‐bacterial anti‐inflammation efficacies urgently needed. Antibiotics the main treatment strategy for infections. excessive use of antibiotics throughout body can cause serious side effects. In addition, miRNA‐based therapeutics superior wounds, but their rapid degradation poor cellular uptake limit clinical application. Tetrahedral framework DNA (tFNA) is an ideal drug delivery system owing to its excellent stability remarkable transport ability. Herein, novel multi‐functional miRNA antibiotic co‐delivery based tFNA presented first time, called B/L. B/L heightened resistance serum codelivery After transdermal administration, specifically target TNF receptor‐associated factor 6(TRAF6) IL‐1receptor‐associated kinase 1(IRAK1), thereby regulating nuclear kappa‐B (NF‐𝜿B) thus effectively reducing inflammation promoting healing infected wounds. This provides versatile, simple, biocompatible, powerful platform personalized multiple diseases.

Language: Английский

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Stimulus-Responsive Four-Stranded DNA Nanoring Assembly to Host Multiple Nanosilver Clusters for Cooperatively Enhanced Fluorescence Biosensing

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(26), P. 10677 - 10685

Published: June 18, 2024

Exploring the ability of four-stranded DNA nanorings (

Language: Английский

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A Tetrahedral Framework DNA-Based Bioswitchable miR-150 Delivery System for Sepsis

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(43), P. 58477 - 58488

Published: Oct. 18, 2024

Sepsis is a disease with high morbidity and mortality, for which effective treatments are lacking. In recent years, microRNAs (miRs) have been shown to regulate numerous biological processes can function as therapeutic options various diseases. However, the poor stability cell entry properties of miRs greatly limited their clinical application. this study, we developed tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) deliver miR-150 treatment sepsis. BiRDS showed anti-inflammatory effects both in vitro vivo by regulating NF-κB Notch1 pathways. Therefore, holds promise an ideal candidate tackling systemic inflammation multiorgan dysfunction septic patients future.

Language: Английский

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