Tetrahedral Framework Nucleic Acids Reverse New-Onset Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is caused by breakdowns of central and peripheral immune tolerance and destructions of insulin-producing β-cells. Conventional insulin injection cannot cure the disease. Regulatory immune cells, including regulatory T-cells (Tregs) and regulatory B-cells (Bregs), play critical roles in immune tolerance. Inducing regulatory immune cells to halt the progress of T1D and restore immune tolerance is the promising approach in T1D immunotherapy. Here, tetrahedral framework nucleic acids (tFNAs) were utilized to treat T1D in non-obese diabetic (NOD) mice. 250 nM tFNA treatment was adopted in the experiment to reverse hyperglycemia and protect insulin-secreting β-cells in diabetic NOD mice. In addition, 250 nM tFNA treatment could induce Tregs and Bregs and suppress helper T (Th)-cells in the pancreas. In the pancreas, cytokines, as a significant signal during CD4+ T-cell differentiation, directly direct the differentiation programs. Apart from cytokines directing the differentiation of T-cells, the signal transducer and activator of transcription (STAT) signal is strongly associated with T-cell differentiation and T1D progression. We demonstrated tFNA treatment inducing regulatory immune cells probably by increasing TGF-β levels and the STAT signal. To sum up, 250 nM tFNA treatment could protect the diabetic NOD mice from hyperglycemia and preserve the functions of β-cells by restoring peripheral immune tolerance. The possible mechanism of inducing immune tolerance was related to the STAT signal and cytokine changes in the pancreas. Moreover, immunoregulation capabilities of tFNAs were demonstrated in the experiment, which set the foundation of tFNAs participating in further antigen-specific immunotherapies.

Tetrahedral Framework Nucleic Acids Can Alleviate Taurocholate-Induced Severe Acute Pancreatitis and Its Subsequent Multiorgan Injury in Mice

“…Here an 8% polyacrylamide gel electrophoresis (PAGE) was used to illustrate that tFNAs were successfully synthesized (Figure b). The molecular mass of tFNAs was shown to be around 200 base pairs (bp) using marker as a reference, consistent with our former findings. ,− TEM was employed to demonstrate the shape of tFNAs, resembling a triangle on a two-dimensional scale (Figure c). The ζ-potential result of tFNAs showed a negative surface charge of 6.967 ± 1.207 mV (Figure d), and dynamic light scattering showed that the average size of tFNAs was approximately 10 nm (Figure e).…”

“…Recent accumulating evidence has indicated that tFNAs possessed a strong capacity in regulating cellular biological behaviors including proliferation, migration, apoptosis, and autophagy. tFNAs were also proved to possess extraordinary anti-inflammatory and antiapoptotic capability in former studies and were utilized in animal models to treat a wide variety of diseases. − According to our previous studies, tFNAs were used to tackle acute kidney injury (AKI) and showed remarkable capacity in rescuing kidney tissue, according to the significant changes observed in various parameters of renal function . Mi Zhou and others in 2020 also proved that tFNAs treatment could alleviate inflammation both in vitro and in model animals with periodontitis, a well-recognized leading cause for tooth loss worldwide …”

Tetrahedral-Framework Nucleic Acid Loaded with MicroRNA-155 Enhances Immunocompetence in Cyclophosphamide-Induced Immunosuppressed Mice by Modulating Dendritic Cells and Macrophages

“…Experiments were carried out as described above. , See the Supporting Information for the specific experimental methods.…”

Smart Drug Delivery Systems Based on DNA Nanotechnology

“…Apart from cancer treatments, the potential of DNA nanostructures in the treatment of other diseases (e. g., inflammatory and degenerative diseases) has also been extensively explored. In recent years, Lin′s research group has designed a series of tetrahedral frame nucleic acids (tFNA)‐based DNA nanostructures for treatment of different diseases, including new‐onset type 1 diabetes, [109] acute gouty arthritis, [110] intracranial hemorrhage, [111] demyelinating diseases, [112] and so on, achieving remarkably therapeutic effects [113] . Notably, they found tFNA has the intrinsic ability to prevent neuronal apoptosis via blocking the TLR2‐MyD88‐NF‐κB signaling pathway, which could efficiently alleviate the acute ischemic stroke [114] …”