Topical siRNA therapy of diabetic-like wound healing
Language English Country England, Great Britain Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
39630486
DOI
10.1039/d4tb01547a
Knihovny.cz E-resources
- MeSH
- Administration, Topical MeSH
- Diabetes Mellitus, Experimental * MeSH
- Wound Healing * drug effects MeSH
- RNA, Small Interfering * administration & dosage genetics pharmacology MeSH
- Matrix Metalloproteinase 9 metabolism genetics MeSH
- Mice MeSH
- Bandages MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA, Small Interfering * MeSH
- Matrix Metalloproteinase 9 MeSH
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.
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 Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague 4 Czechia
Technical University of Liberec Faculty of Health Studies Trebizskeho 1402 46001 Liberec Czechia
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