Antioxidative and Angiogenesis-Promoting Effects of Tetrahedral Framework Nucleic Acids in Diabetic Wound Healing with Activation of the Akt/Nrf2/HO-1 Pathway

Abstract

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.

LPS-stimulated Macrophage Exosomes Inhibit Inflammation by Activating the Nrf2 / HO-1 Defense Pathway and Promote Wound Healing in Diabetic Rats

“…In the current treatment, the wound healing of diabetes can not be improved [30][31][32]. After the trauma, it will lead to a series of diseases, leading to chronic in ammation and the production of a large number of reactive oxygen species [33,34]. At the same time, it will lead to a large number of endothelial cell apoptosis and collagen synthesis reduction, and the formation of blood vessels is blocked [4].So we are eager to nd a new treatment.…”

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing

“…Framework nucleic acids (FNAs) – biocompatible and biodegradable nucleic acids – show advantages in tailorable functionality and multiple modifiability, which can be applied to drug delivery and nanomedicine ( Lin et al, 2020 ). Lin et al (2020) demonstrated that framework nucleic acids (tFNAs) attenuated inflammation, prevented oxidative damage, and promoted angiogenesis in diabetic wound healing.…”

The immune regulatory effects of tetrahedral framework nucleic acid on human T cells via the mitogen‐activated protein kinase pathway

“…As a novel nanoscale material, tetrahedral framework nucleic acid (TFNA) is composed of four editable isometric single‐strand DNA (ssDNA) molecules, which could self‐assemble and form a stable three‐dimensional DNA nanostructure with excellent endocytotic properties 7,8 . Additionally, the multi‐biological activities of TFNA have already been revealed 9‐12 . For instance, TFNA could polarize tissue‐resident macrophages from M1 to M2 phenotypes that promotes the recovery of bisphosphonates‐mediated jaw osteonecrosis in mice 13 .…”

“… 7 , 8 Additionally, the multi‐biological activities of TFNA have already been revealed. 9 , 10 , 11 , 12 For instance, TFNA could polarize tissue‐resident macrophages from M1 to M2 phenotypes that promotes the recovery of bisphosphonates‐mediated jaw osteonecrosis in mice. 13 Similarly, TFNA significantly down‐regulates IL‐1β and IL‐6 secretion by LPS‐induced macrophages in attenuating bacterial inflammation.…”