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

Yichen Yang,

Ziqi Yue

et al.

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

Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids DOI Creative Commons
Junjie Gu,

Jiale Liang,

Taoran Tian

et al.

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

Citations

2
Tetrahedral Framework Nucleic Acid‐Based Delivery of DJ‐1‐saRNA Prevent Retinal Ischaemia–Reperfusion Injury via Inhibiting Ferroptosis DOI Creative Commons

Xianggui Zhang,

Zilong Deng, Xiaoxiao Xu

et al.

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

ABSTRACT Retinal ischaemia/reperfusion injury (RI/RI) is the primary pathophysiological mechanism underlying retinal ischaemic diseases, potentially resulting in significant and irreversible visual impairment. Currently, there are no effective treatments available for RI/RI, oxidative stress a critical factor that contributes to associated damage. DJ‐1, an important endogenous antioxidant, has been proposed as promising therapeutic agent RI/RI owing its potential overexpression. In this study, tetrahedral frame nucleic acids (tFNAs) were utilised delivery vehicle DJ‐1 small activating RNA (saRNA), synthesis of novel nanocomposite (tFNAs‐DJ‐1‐saRNA). vitro experiments demonstrated tFNAs effectively delivered DJ‐1‐saRNA R28 cells, thus exerting repair effect on injury. vivo investigations revealed intravitreal injection tFNAs‐DJ‐1‐saRNA facilitated gene expression mitigated atrophy induced by RI/RI. Mechanistically, activated xCT/GPX4 pathway, thereby inhibiting ferroptosis, reducing ganglion cell damage protecting tissue. conclusion, study complex can ameliorate suggesting treatment diseases.

Language: Английский

Citations

1
Therapeutic effects of tetrahedral framework nucleic acids and tFNAs‐miR22 on retinal ischemia/reperfusion injury DOI Creative Commons
Xiaoxiao Xu, Yanyan Fu, Hongmei Luo

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(11)

Published: July 31, 2024

Abstract Retinal ischemia/reperfusion injury (RI/R) is a common pathological process in ophthalmic diseases, which can cause severe visual impairment. The mechanisms underlying RI/R damage and repair are still unclear. Scholars actively exploring effective intervention strategies to restore impaired function. With the development of nucleic acid nanomaterials, tetrahedral framework acids (tFNAs) have shown promising therapeutic potential various fields such as stem cells, biosensors, tumour treatment due their excellent biological properties. Besides, miRNA‐22‐3p (miR‐22), an important regulatory factor neural tissue, has been proven positive effects neurodegenerative diseases. By stably constructing complex miR22 (tFNAs‐miR22), we observed that tFNAs‐miR22 had effect on retinal tissue. Previous studies tFNAs effectively deliver miR‐22 into damaged neurons, subsequently exerting neuroprotective effects. Interestingly, found there was certain synergistic between miR‐22. selectively activated ERK1/2 signalling pathway reduce neuronal apoptosis, accelerate cell proliferation, synaptic functional activity. In this study, established simple yet small molecule drug for may become neuroprotectant treating type vision impairment disease future.

Language: Английский

Citations

6
Targeted siRNA Delivery Against RUNX1 Via tFNA: Inhibiting Retinal Neovascularization and Restoring Vessels Through Dll4/Notch1 Signaling DOI Creative Commons

Xiaodi Zhou,

Xiaoxiao Xu, Qiong Wang

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(3), P. 39 - 39

Published: March 19, 2025

To assess the efficacy of tetrahedral framework nucleic acids (tFNAs) as a delivery system for small interfering RNA (siRNA) targeting RUNX1 (siRUNX1) in inhibiting retinal neovascularization (RNV) and restoring vascular integrity via Dll4/Notch1 signaling pathway. tFNAs tFNAs-siRUNX1 were synthesized using annealing single-stranded DNAs characterized by PAGE high-performance capillary electrophoresis. Human umbilical vein endothelial cells treated under hypoxic conditions with tFNAs-siRUNX1, cellular uptake was evaluated fluorescence microscopy flow cytometry. Angiogenesis assessed through EdU proliferation, tube formation, wound-healing assays. In vivo experiments used oxygen-induced retinopathy (OIR) laser-induced choroidal (CNV) models mice, subsequent imaging optical coherence tomography (OCT) fundus angiography. Gene protein expression analyzed RT-PCR Western blotting, focusing on pathway apoptosis markers. effectively inhibited cell migration, formation vitro. OIR CNV models, it reduced neovascularization, nonperfusion areas, leakage. The mechanism involved modulation pathway, decreased Dll4, Notch1, Hes1 increased Nts expression. also Bcl-2/Bax is promising RNV, integrity, providing potential therapeutic alternative to anti-VEGF treatments.

Language: Английский

Citations

0
Selenium nanoparticles attenuate retinal pathological angiogenesis by disrupting cell cycle distribution DOI

Zheng Nie,

Yongxuan Liu, Xu Li

et al.

Nanomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: March 21, 2025

This study aims to explore the mechanism by which selenium nanoparticles (SeNPs) inhibit retinal neovascularization (RNV) and identify a more effective treatment for pathological RNV. The characterization identification of synthesized were conducted investigate their effects on function human umbilical vein endothelial cells (HUVECs), blood vessel development in mice, impact oxygen-induced retinopathy. Tritium-labeled thymine was utilized label newly DNA both vivo vitro, allowing observation SeNPs' cell proliferation. Additionally, flow cytometry, immunofluorescence, western blotting techniques employed elucidate mechanisms SeNPs neovascularization. can significantly functions vascular cells, particularly proliferation, vitro. achieve this modulating expression cycle-related proteins through regulation PI3K-AKT-p21 axis, turn inhibits transition cycle from G1 phase S phase. may be novel interference

Language: Английский

Citations

0
A Noninvasive Nanoeyedrop Therapy for the Inhibition of Uveal Melanoma: Tetrahedral Framework Nucleic Acid–Based Bioswitchable MicroRNA Delivery System DOI
Jiang Zhou,

Yichen Yang,

Ziqi Yue

et al.

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

Citations

0