Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.

Department of Physical Chemistry University of Chemistry and Technology Prague Technicka 5 166 28 Prague 6 Czechia

Faculty of Biomedical Engineering Czech Technical University Prague Namesti Sitna 3105 Kladno 2 272 01 Czechia

Faculty of Science Charles University Hlavova 2030 Prague 2 128 40 Czechia

InoCure s r o Politickych veznu 13 100 00 Prague Czechia

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czechia

Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague 4 Czechia

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo namesti 2 166 10 Prague 6 Czechia

Technical University of Liberec Faculty of Health Studies Trebizskeho 1402 46001 Liberec Czechia

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