Gouty arthritis is a very familiar inflammatory arthritis. Controlling inflammation is the key to preventing gouty arthritis. However, colchicine, the most highly represented drug used in clinical practice, has strict contraindications owing to some severe side effects. Curcumin (Cur), a natural anti-inflammatory drug, has demonstrated good safety and efficacy. However, the rapid degradation, poor aqueous solubility, and low bioavailability of Cur limit its therapeutic effect. To strengthen the effectiveness and bioavailability of Cur. Cur loaded tetrahedral framework nucleic acids (Cur-TFNAs) were synthesized to deliver Cur. Compared with free Cur, Cur-TFNAs exhibit a preferable drug stability, good biocompatibility (CCK-8 assay), ease of uptake (immunofluorescence), and higher tissue utilization (in vivo biodistribution). Most importantly, Cur-TFNAs present better antiinflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression. Therefore, we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.Peer review under responsibility of KeAi Communications Co., Ltd.
Currently available strategies show limited effects in preventing morbidity and disability from chronic diabetic wounds. Ideal vascularization is indispensable for better restoration and prognosis of diabetic wounds. This study aims to investigate the role of tetrahedral framework nucleic acids (tFNAs) in the process of angiogenesis during diabetic wound healing and the underlying mechanism. The in vitro results showed that tFNAs treatment enhanced the formation of a vessel-like structure that was inhibited by advanced glycation end products (AGEs). Positive variations were detected in aspects of cell viability, migratory ability, nitric oxide (NO) levels, and vascular endothelial growth factor-A (VEGF-A) expression. In addition, high reactive oxygen species (ROS) levels and gene expressions relevant to oxidative damage and inflammation in diabetic human umbilical vein endothelial cells (HUVECs) were attenuated by tFNAs. As for the underlying mechanism, the p-Akt/total Akt ratio, nuclear factor erythroid 2-related factor 2 (Nrf2) levels, and heme oxygenase-1 (HO-1) levels were higher in diabetic HUVECs treated with tFNAs. In vivo experiments showed that tFNAs facilitated diabetic wound healing by accelerating vascularization, epithelialization, collagen deposition, and collagen alignment. In conclusion, tFNAs could protect endothelial cell function, reduce inflammation, and impede oxidative damage through their antioxidant activity via the Akt/Nrf2/HO-1 signaling pathway. The application of tFNAs may pave the way for better healing of diabetic wounds.
While the skin is considered the first line of defense in the human body, there are some vulnerabilities that render it susceptible to certain threats, which is an issue that is recognized by both patients and doctors. Cutaneous wound healing is a series of complex processes that involve many types of cells, such as fibroblasts and keratinocytes. This study showed that tetrahedral framework nucleic acids (tFNAs), a type of self-assembled nucleic-acid material, have the ability to promote keratinocyte(HaCaT cell line) and fibroblast(HSF cell line) proliferation and migration in vitro. In addition, tFNAs increased the secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in HSF cells and reduced the production of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in HaCaT cells by activating the AKT-signaling pathway. During in vivo experiments, tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars, compared with the control treatment that did not use tFNAs. This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring, which indicates the potential application of tFNAs in skin tissue regeneration.
Retinal ischemia-reperfusion (I/R) injuries are involved in the universal pathological processes of many ophthalmic diseases, including glaucoma, diabetic retinopathy, and retinal arterial occlusion.
siRNA is found to effectively knock down the target gene in cells, which is considered a promising strategy for gene therapy. However, the application of siRNA is limited due to its low efficiency of the cellular uptake. Tetrahedral framework nucleic acids (tFNAs) are synthesized by four single-stranded DNAs and show multiple biological functions in recent studies, especially suitable for drug delivery. More than 60% of malignant melanomas are associated with Braf gene mutation, an attractive therapeutic target for RNA interference. In this study, we modified anti-Braf siRNA (siBraf) with tFNAs to downregulate the target gene. Meanwhile, we directly incorporated AS1411 (a DNA aptamer) to our nanostructure, which assists tFNAs to improve the cellular uptake efficacy of siBraf significantly. The results indicated that tFNAs-AS1411-siBraf exhibited more potent activity to cleave Braf mRNA than free siBraf. This study may provide a new idea for the combination therapy of siRNA and aptamers via DNA nanomaterials to achieve gene silencing.
Acute myocardial infarction, which can be extremely difficult to treat, is the worst deadly disease around the world. Reperfusion is expedient to reverse myocardial ischemia. However, during reperfusion, reactive oxygen species (ROS) produced by myocardial ischemia-reperfusion injury (MIRI) and further cell apoptosis are the most serious challenges to cardiomyocytes. Therefore, searching for reagents that can simultaneously reduce oxidative damage and MIRI-induced apoptosis is the pivotal strategy to rescue injured cardiomyocytes. Nevertheless, current cardioprotective drugs have some shortcomings, such as cardiotoxicity, inadequate intravenous administration, or immature technology. Previous studies have shown that tetrahedral DNA nanostructures (TDNs) have biological safety with promising anti-inflammatory and antioxidative potential. However, the progress that TDNs have made in the biological behavior of cardiomyocytes has not been explored. In this experiment, a cellular model of MIRI was first established. Then, confirmed by a series of experiments, our study indicates that TDNs can significantly decrease oxidative damage and apoptosis by limiting the overexpression of ROS, along with effecting the expression of apoptosis-related proteins. In addition, Western blot analysis demonstrated that TDNs could activate the Akt/Nrf2 signaling pathway to improve the myocardial injury induced by MIRI. Above all, the antioxidant and antiapoptotic capacities of TDNs make them a potential therapeutic drug for MIRI. This study provides new ideas and directions for more homogeneous diseases induced by oxidative damage.
Parkinson’s disease (PD) is a neurodegenerative disease characterized by a series of progressive motor disorders. PD is caused by dysfunction of basal ganglia, decrease of dopaminergic neurons in substantia nigra, and abnormal accumulation of Lewy bodies and Lewy neurites. Antiparkinsonian agents, which are currently used for treatment of PD, exhibit unsatisfactory effects on disease control. In recent years, tetrahedral framework nucleic acids (TFNAs) have been considered as multifunctional nanomaterials, and their scope of application has been extended to a wide range of areas. In previous studies, TFNAs were shown to exert positive effects on various cell types in processes such as cell proliferation, cell differentiation, and apoptosis. In the present study, we explored the role of TFNAs in the treatment and prevention of PD in vitro and elucidated its underlying mechanisms of action. On the basis of the experiments conducted, we demonstrated that TFNAs could inhibit and repair the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of PC12 cells through decreasing the accumulation of α-synuclein, one of the characteristic biomarkers of PD. Genes and proteins related to the AKT/PI3K signaling and mitochondrial apoptotic pathways were examined to further support this finding. Most importantly, TFNAs exhibited unexpected neuroprotective and neurorestorative effects on PC12 cells, providing a novel approach for reducing the neuropathological changes caused by PD.
Parkinson's disease (PD) is the most common chronic neurodegenerative disease and is characterized by motor dysfunctions. Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of the neurotoxicity that causes PD. As an inhibitor of LRRK2 activity, vitamin B12 (VB12) is a promising therapeutic option for PD and is shown to restore autophagy in PD models. However, the dependence on transporters and the extremely low brain tissue utilization of VB12 limit its therapeutic effects. Based on this, VB12-loaded tetrahedral framework nucleic acid (TVC) is synthesized and its effectiveness in the model of PD induced with 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine is evaluated. TVC provides better recovery of autophagy than free VB12 did both in vivo and in vitro, leading to enhanced clearing of abnormal protein accumulations and restoration of PD motor symptoms. It is believed that TVC has broad therapeutic potential in the treatment of PD and similar neurodegenerative diseases.
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