Tetrahedral framework nucleic acids‐based delivery promotes intracellular transfer of healing peptides and accelerates diabetic would healing

Abstract

Objectives Peptide‐based therapeutics are natural candidates to desirable wound healing. However, enzymatic surroundings largely limit its stability and bioavailability. Here, we developed a tetrahedral framework nucleic acids(tFNA)‐based peptide delivery system, that is, p@tFNAs, to address deficiencies of healing peptide stability and intracellular delivery in diabetic wound healing. Materials and Methods AGEs (advanced glycation end products) were used to treat endothelial cell to simulate cell injury in diabetic microenvironment. The effects and related mechanisms of p@tFNAs on endothelial cell proliferation, migration, angiogenesis and ROS (reactive oxygen species) production have been comprehensively studied. The wound healing model in diabetic mice was photographically and histologically investigated in vivo. Results Efficient delivery of healing peptide by the framework(tFNA) was verified. p@tFNAs helped overcome the angiogenic obstacles induced by AGEs via ERK1/2 phosphorylation. In the meantime, p@tFNA exhibited its antioxidative property to achieve ROS balance. As a result, p@tFNA improved angiogenesis and diabetic wound healing in vitro and in vivo. Conclusions Our findings demonstrate that p@tFNA could be a novel therapeutic strategy for diabetic wound healing. Moreover, a new method for intracellular delivery of peptides was also constructed.

Tetrahedral Framework Nuclear Acids Can Regulate Interleukin-17 Pathway to Alleviate Inflammation and Inhibit Heterotopic Ossification in Ankylosing Spondylitis

“…Due to the source of its components, tFNAs are highly programmable and easy to modify and label with very low immunogenicity. Recently, studies have found that tFNAs can penetrate different cells to affect their various biological activities. − Moreover, our previous research has found that tFNAs or its derivatives could inhibit inflammation via regulating the IL-17 pathway. , Li and his colleagues discovered that tFNAs loaded with resveratrol could suppress inflammation and ameliorate insulin resistance via inhibiting Th1 and Th17 cell activation to reduce the production of IL-17 . In our study, tFNAs were used as a treatment option for AS, and significant therapeutic effects were observed both in vivo and in vitro .…”

“…Tetrahedral frame nucleic acids (tFNAs) are bioactive nanomaterial with tetrahedron-like structures that have been widely studied in the biomedical field. − Its editability allows it to carry coding sequence in a framework structure for the treatment of specific diseases. The small size and the negative surface potential of tFNAs determine that it could be quickly ingested by cells to exert various biological effects.…”

Enhanced Electrochemical Characterization of the Immune Checkpoint Protein PD‐L1 using Aptamer‐Functionalized Magnetic Metal‐Organic Frameworks

“…[35][36][37] The 3.5% agarose gel electrophoresis (Figure 5C) also demonstrated that NTH consists of four ssDNA molecules. [38][39][40] By dynamic light scattering (DSL), the diameter of the NTH was measured uniformly as 13.54 nm (Figure 5D). In Figure 5E and Figure S8, Supporting Information, we illustrate that NTH exhibits a better support effect on the electrode surface than single-stranded aptamers by comparing their current values when detecting the target.…”

Framework nucleic acids as promising reactive oxygen species scavengers for anti-inflammatory therapy

“…Statistics showed that modification with healing peptide not only further strengthened the ROS-scavenging ability of simple tFNAs from 0.03-fold to 0.67-fold, but also elevated the phosphorylation of ERK1/2 to 1.49-fold, therefore improving the angiogenesis and wound closure processes. 79 Although extensive research studies have confirmed that stable and biocompatible tetrahedral DNA nanostructures are naturally endowed with the ability to neutralize ROS and trigger a rather wide range of cytoprotective pathways, including Akt/Nrf2/HO-1, BCL2/BAX/caspase-3, MAPK/ERK, and NF-κB signaling, the specific trigger mechanism still requires further investigation. First, due to the complicated interaction between ROS and inflammation, the elimination of ROS by DNA self-oxidation can be considered as an important regulatory factor.…”

“…Statistics showed that modification with healing peptide not only further strengthened the ROS-scavenging ability of simple tFNAs from 0.03-fold to 0.67-fold, but also elevated the phosphorylation of ERK1/2 to 1.49-fold, therefore improving the angiogenesis and wound closure processes. 79…”