1. Topical siRNA therapy of diabetic-like wound healing.
- Author
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Neuhoferova, Eva, Kindermann, Marek, Buzgo, Matej, Vocetkova, Karolina, Panek, Dalibor, Cigler, Petr, and Benson, Veronika
- Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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