One ternary nucleic acid delivery system with smart dextran-peptide coating enables in vivo and ex vivo wound therapy

Abstract

<h2>Summary</h2> Apart from the superiority in supplementing cytokines in wound healing, gene therapy faces several critical obstacles, including the substantial exudation in wounds and difficult-to-transfect primary cells. Herein, a ternary nucleic acid delivery system (HPD) was constructed through the assembly of polyhexamethylene biguanide, DNA, and dextran-peptide conjugate (Dex-H2E5), which are prepared by the highly reproducible reaction of dextran and peptide. The proposed Dex-H2E5 forms a smart coating of HPD and acts as the "propellant" for the nucleic acid delivery. <i>In vitro</i> results confirmed that HPD realized low toxicity and high transfection performance in cell lines/primary cells and favorable serum stability/dosage independence. <i>In vivo</i> and <i>ex vivo</i> therapy of severe skin wounds further demonstrated the excellent performance of HPD after loading a therapeutic plasmid. Our work offers a highly efficient, reproducible delivery system for wound gene therapy. It could be extended to other clinical scenarios in which superior gene therapy is urgently demanded.