A Binary siRNA‐Loaded Tetrahedral DNA Nanobox for Synergetic Anti‐Aging Therapy DOI Open Access
Ziqi Yue, Yichen Yang, Lulingxiao Nie

et al.

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

Published: Dec. 17, 2024

Extensive accumulation of senescent cells contributes to organismal aging, and slowing down the process cellular senescence may ameliorate age-related pathologies. Targeted inhibition mechanistic target rapamycin complex 1 (mTORC1) is found suppress conversion senescence. The regulatory-associated protein mTOR (Raptor), a key component mTORC1, has been implicated as important in aging process, its druggability deserves be investigated. Due high efficiency convenience drug construction, siRNA shows great potential silencing Raptor expression via RNA interfering therapy. Here, we developed functionalized anti-aging nanoplatform based on tetrahedral DNA nanostructures (TDNs) encapsulating targeting for synergistic therapy, named siR-TDN

Language: Английский

A bioswitchable delivery system for microRNA therapeutics based on a tetrahedral DNA nanostructure DOI
Songhang Li, Taoran Tian, Tao Zhang

et al.

Nature Protocols, Journal Year: 2024, Volume and Issue: 20(2), P. 336 - 362

Published: Aug. 30, 2024

Language: Английский

Citations

33
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
Treatment of liver fibrosis: Past, current, and future DOI Open Access
Chunye Zhang, Shuai Liu, Ming Yang

et al.

World Journal of Hepatology, Journal Year: 2023, Volume and Issue: 15(6), P. 755 - 774

Published: June 25, 2023

Liver fibrosis accompanies the progression of chronic liver diseases independent etiologies, such as hepatitis viral infection, alcohol consumption, and metabolic-associated fatty disease. It is commonly associated with injury, inflammation, cell death. characterized by abnormal accumulation extracellular matrix components that are expressed myofibroblasts collagens alpha-smooth actin proteins. Activated hepatic stellate cells contribute to major population myofibroblasts. Many treatments for have been investigated in clinical trials, including dietary supplementation (e.g., vitamin C), biological treatment simtuzumab), drug pegbelfermin natural herbs), genetic regulation non-coding RNAs), transplantation stem hematopoietic cells). However, none these has approved Food Drug Administration. The efficacy can be evaluated histological staining methods, imaging serum biomarkers, well scoring systems, fibrosis-4 index, aspartate aminotransferase platelet ratio, non-alcoholic disease score. Furthermore, reverse slowly frequently impossible advanced or cirrhosis. To avoid life-threatening stage fibrosis, anti-fibrotic treatments, especially combined behavior prevention, treatment, drugs herb medicines, needed. This review summarizes past studies current future fibrosis.

Language: Английский

Citations

40
A Bioswitchable MiRNA Delivery System: Tetrahedral Framework DNA-Based miRNA Delivery System for Applications in Wound Healing DOI
Xiaoying Lyu,

Haoyan Wu,

Mengzhuo Xu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(26), P. 33192 - 33204

Published: June 17, 2024

The human body's primary line of defense, the skin, is especially prone to harm. Although microRNA (miRNA)-based therapies have attracted increasing attention for skin wound healing, their applications remain limited owing a range issues. Tetrahedral framework DNA (tFNA), nanomaterial possessing nucleic acid characteristics, exhibits an excellent biocompatibility, in addition anti-inflammatory and transdermal delivery capabilities, can accelerate healing. Due its potential exert synergistic action with therapeutic miRNA, tFNA has been considered ideal vehicle miRNA therapy. design synthesis bioswitchable system (BiRDS) reported, which contains three miRNAs as well core maximize loading capacity while preserving characteristics tFNA. A high stability, permeability cells tissues good biological compatibility are demonstrated. By selectively inhibiting heparin-binding epidermal growth factor (HB-EGF), BiRDS inhibit NF-κB pathway simultaneously controlling PTEN/Akt pathway. As result, helps healing go through inflammation proliferative phase. This study demonstrates advantages miRNA-based therapy provides new research ideas treatment skin-related diseases.

Language: Английский

Citations

10
Framework nucleic acids as promising reactive oxygen species scavengers for anti-inflammatory therapy DOI
Yujie Zhu, Ruijianghan Shi, Weitong Lu

et al.

Nanoscale, Journal Year: 2024, Volume and Issue: 16(15), P. 7363 - 7377

Published: Jan. 1, 2024

Framework nucleic acid nanomaterials possess excellent antioxidative and anti-inflammatory therapeutic properties through scavenging reactive oxygen species.

Language: Английский

Citations

9
Cutting-edge biotherapeutics and advanced delivery strategies for the treatment of metabolic dysfunction-associated steatotic liver disease spectrum DOI
Juhyeong Hong, Yong‐Hee Kim

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 433 - 456

Published: Feb. 11, 2025

Language: Английский

Citations

1
Macrophages and platelets in liver fibrosis and hepatocellular carcinoma DOI Creative Commons
Martina Casari,

Dominik Siegl,

Carsten Deppermann

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 5, 2023

During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver this leads to the loss hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility infection. At an early stage, fibrosis is a dynamic reversible process, however, from cirrhotic there significant progression hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) monocyte-derived are important drivers progression, but can also induce its regression once triggers chronic inflammation eliminated. cancer, they attracted tumor site become tumor-associated (TAMs) polarized towards M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis hemostasis, platelets stimulate development by secreting profibrogenic factors regulating innate immune response, e.g., interacting with monocytes macrophages. Here, we review recent literature on interplay

Language: Английский

Citations

19
Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis? DOI Creative Commons
Yushu Yang, Xiaosong He, Manuel Rojas

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 30, 2023

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, injuries, fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC multifactorial involves immune dysregulation, abnormal bile metabolism, progressive ultimately leading to cirrhosis failure. Ursodeoxycholic acid (UDCA) obeticholic (OCA) are currently used as first- second-line treatments, respectively. However, many patients do not respond adequately UDCA, the long-term effects these drugs limited. Recent research has advanced our understanding mechanisms in greatly facilitated development novel target mechanistic checkpoints. Animal studies clinical trials pipeline have yielded promising results slowing progression. Targeting mediated anti-inflammatory therapies focused on early stage, while anti-cholestatic anti-fibrotic emphasized late stage disease, which fibrosis development. Nonetheless, it worth noting that currently, there exists a dearth therapeutic options can effectively impede progression its terminal stages. Hence, urgent need for further aimed at investigating underlying pathophysiology with potential effects. This review highlights current knowledge immunological cellular PBC. Further, we also address mechanism-based strategies improve efficacy existing treatments.

Language: Английский

Citations

16
RNA Nanomedicine: Delivery Strategies and Applications DOI

Junho Byun,

Yina Wu,

Jin-Won Park

et al.

The AAPS Journal, Journal Year: 2023, Volume and Issue: 25(6)

Published: Oct. 2, 2023

Language: Английский

Citations

13
C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape DOI Creative Commons

Yangkun Guo,

Chong Zhao,

Wenting Dai

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(8), P. 2572 - 2587

Published: Jan. 1, 2023

The accumulation of extracellular matrix (ECM) proteins in the liver leads to fibrosis and end-stage cirrhosis.C-C motif chemokine receptor 2 (CCR2) is an attractive target for treating fibrosis.However, limited investigations have been conducted explore mechanism by which CCR2 inhibition reduces ECM fibrosis, focus this study.Liver injury were induced carbon tetrachloride (CCl4) wild-type mice Ccr2 knockout (Ccr2 -/-) mice.CCR2 was upregulated murine human fibrotic livers.Pharmacological with cenicriviroc (CVC) reduced prevention treatment administration.In single-cell RNA sequencing (scRNA-seq), CVC demonstrated alleviate restoring macrophage neutrophil landscape.CVC administration deletion can also inhibit hepatic inflammatory FSCN1 + macrophages HERC6 neutrophils.Pathway analysis indicated that STAT1, NFκB, ERK signaling pathways might be involved antifibrotic effects CVC.Consistently, decreased phosphorylated liver.In vitro, could transcriptionally suppress crucial profibrotic genes (Xaf1, Slfn4, Slfn8, Ifi213, Il1β) inactivating STAT1/NFκB/ERK pathways.In conclusion, study depicts a novel alleviates immune cell gene transcription via CCR2-STAT1/NFκB/ERK pathways.

Language: Английский

Citations

11