Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Macrophage Reprogramming Into a Pro-Healing Phenotype by Sirna Delivered With Lbl Assembled Nanocomplexes for Wound Healing Applications Publisher Pubmed



Sharifiaghdam M1, 2 ; Shaabani E1, 2 ; Sharifiaghdam Z3 ; De Keersmaecker H1, 4 ; Lucas B1 ; Lammens J5 ; Ghanbari H2 ; Teimooritoolabi L6 ; Vervaet C5 ; De Beer T7 ; Faridimajidi R2 ; De Smedt SC1 ; Braeckmans K1, 4 ; Fraire JC1
Authors

Source: Nanoscale Published:2021


Abstract

Excessive inflammatory responses in wounds are characterized by the presence of high levels of pro-inflammatory M1 macrophages rather than pro-healing M2 macrophages, which leads to delayed wound healing. Macrophage reprogramming from the M1 to M2 phenotype through knockdown of interferon regulatory factor 5 (irf5) has emerged as a possible therapeutic strategy. While downregulation of irf5 could be achieved by siRNA, it very much depends on successful intracellular delivery by suitable siRNA carriers. Here, we report on highly stable selenium-based layer-by-layer (LBL) nanocomplexes (NCs) for siRNA delivery with polyethyleneimine (PEI-LBL-NCs) as the final polymer layer. PEI-LBL-NCs showed good protection of siRNA with only 40% siRNA release in a buffer of pH = 8.5 after 72 h or in simulated wound fluid after 4 h. PEI-LBL-NCs also proved to be able to transfect RAW 264.7 cells with irf5-siRNA, resulting in successful reprogramming to the M2 phenotype as evidenced by a 3.4 and 2.6 times decrease in NOS-2 and TNF-α mRNA expression levels, respectively. Moreover, irf5-siRNA transfected cells exhibited a 2.5 times increase of the healing mediator Arg-1 and a 64% increase in expression of the M2 cell surface marker CD206+. Incubation of fibroblast cells with conditioned medium isolated from irf5-siRNA transfected RAW 264.7 cells resulted in accelerated wound healing in an in vitro scratch assay. These results show that irf5-siRNA loaded PEI-LBL-NCs are a promising therapeutic approach to tune macrophage polarization for improved wound healing. © The Royal Society of Chemistry.
Other Related Docs
5. Current Advances in Wound Healing and Regenerative Medicine, Current Stem Cell Research and Therapy (2024)
8. New Concepts in Wound Targeting Through Liposome-Based Nanocarriers (Lbns), Journal of Drug Delivery Science and Technology (2022)
11. Modulation of Macrophage Polarization for Bone Tissue Engineering Applications, Iranian Journal of Allergy# Asthma and Immunology (2018)
18. Recent Advances in Sirna Delivery Systems for Prostate Cancer Therapy, Current Pharmaceutical Biotechnology (2022)
20. Small Interfering Rnas (Sirnas) in Cancer Therapy: A Nano-Based Approach, International journal of nanomedicine (2019)