NANOFIBER DRESSING CONSISTING OF ANTISENSE RNA-FUNCTIONALIZED NANODIAMONDS FOR THERAPY OF NON-HEALING WOUNDS IN DIABETIC INDIVIDUALS

1 NEUHÖFEROVÁ Eva
Co-authors:
2 PETRÁKOVÁ Vladimíra 2 VOCETKOVÁ Karolína 1 KINDERMANN Marek 1 KŘIVOHLAVÁ Romana 1,2 BENSON Veronika
Institutions:
1 Institute of Microbiology, Czech Academy of Sciences, Czech Republic, EU
2 Czech Technical University in Prague, Faculty of Biomedical Engineering, Czech Republic, EU
Conference:
9th International Conference on Nanomaterials - Research & Application, Hotel Voronez I, Brno, Czech Republic, EU, October 18th - 20th 2017
Proceedings:
Proceedings 9th International Conference on Nanomaterials - Research & Application
Pages:
467-472
ISBN:
978-80-87294-81-9
ISSN:
2694-930X
Published:
8th March 2018
Proceedings of the conference were published in Web of Science and Scopus.
Metrics:
40 views / 5 downloads
Abstract

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.Our results suggest that using nanodiamond-siRNA complexes with nanofiber-controlled and localized release is a promising approach in gene therapy of non-healing wounds.

Keywords: Electrospun nanofibers, fluorescent nanodiamonds, RNA interference, gene therapy, non-healing wounds.
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