Nanofiber dressing consisting of antisense rna-functionalized nanodiamonds for therapy of non-healing wounds in diabetic individuals

0499508 - MBÚ 2019 RIV CZ eng C - Konferenční příspěvek (zahraniční konf.)
Neuhoferová, Eva - Petráková, V. - Vocetková, K. - Kindermann, Marek - Křivohlavá, Romana - Benson, Veronika
Nanofiber dressing consisting of antisense rna-functionalized nanodiamonds for therapy of non-healing wounds in diabetic individuals.
CONFERENCE PROCEEDINGS NANOCON 2017. Brno: Tnager Ltd., 2018, s. 467-472. ISBN 9788087294819.
[9th International Conference on Nanomaterials - Research and Application (NANOCON). Brno (CZ), 18.10.2017-20.10.2017]
Grant CEP: GA MZd(CZ) NV15-33094A
Institucionální podpora: RVO:61388971
Klíčová slova: Electrospun nanofibers * fluorescent nanodiamonds * RNA interference
Obor OECD: Microbiology

Non-healing wounds are serious complication in diabetic patients and represent an attractive challenge for development of suitable carrier system possessing constant and localized release of therapeutic biomolecule into the wound without any undesired side effects. Given the fact that these non-healing wounds are result of impaired balance in metalloproteinases synthesized by immune cells residing the wounds, gene therapy offering knock down of such enzymes is of great interest.
Here we challenged a development of functional and biocompatible wound dressing enabling controlled release of trackable carrier loaded with therapeutic siRNA. Our dressing consists of scaffold from degradable polymer nanofibers enriched with fluorescent nanodiamond particles (FND). We have previously shown the nanodiamond particles are great carriers for antisense RNAs. Their advantages represent high biocompatibility, stable luminescence giving us the possibility to track the carrier system in the wound, and effective release of antisense RNA in the wound. Embedding of nanodiamond-siRNA systems into nanofiber scaffold enables continuous release of siRNA and maintaining the stable siRNA concentration in the wound site resulting in a promotion of wound healing.
We developed FND-siRNA complexes specific to MMP-9 that efficiently inhibit the expression of target MMP-9 mRNA. The complexes were embedded into core/shell nanofibers from PVA and PCL, visualized by confocal microscopy, and characterized by electron microscopy. Real-time PCR was used to assess the silencing effect of siRNA that has been delivered to target murine fibroblasts by FND released from nanofiber dressing. Nanofiber system with embedded FNDs was applied on wounds in diabetic animal models to evaluate its suitability regarding short and long term toxicity, efficacy, and handling in vivo.

Trvalý link: http://hdl.handle.net/11104/0291700