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

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.

Automated summary

In this study, a tetrahedral framework nucleic acids (tFNA)-based peptide delivery system was developed to address the stability and intracellular delivery issues of peptides in diabetic wound healing. The results showed that the delivery system improved angiogenesis and diabetic wound healing in vitro and in vivo, and exhibited antioxidative properties.