NDLI: Sele-targeted siRNA liposome nanoparticles inhibit pathological scars formation via blocking the cross-talk between monocyte and endothelial cells: a preclinical study based on a novel mice scar model

Content Provider	Springer Nature : BioMed Central
Author	Li, Luyu Wang, Yong Meng, Jing Wang, Xue Wu, Xiaojin Wo, Yan Shang, Ying Zhang, Zhen
Abstract	Background Pathological scars (PS) are one of the most common complications in patients with trauma and burns, leading to functional impairments and aesthetic concerns. Mechanical tension at injury sites is a crucial factor in PS formation. However, the precise mechanisms remain unclear due to the lack of reliable animal models. Results We developed a novel mouse model, the Retroflex Scar Model (RSM), which induces PS by applying controlled tension to wounds in vivo. RNA sequencing identified significant transcriptome changes in RSM-induced scars. Elevated expression of E-Selectin (Sele) was observed in endothelial cells from both the RSM model and human PS (Keloid) samples. In vitro studies demonstrated that cyclic mechanical stretching (CMS) increased Sele expression, promoting monocyte adhesion and the release of pro-inflammatory factors. Single-cell sequencing analysis from the GEO database, complemented by Western blotting, immunofluorescence, and co-immunoprecipitation, confirmed the role of Sele-mediated monocyte adhesion in PS formation. Additionally, we developed Sele-targeted siRNA liposome nanoparticles (LNPs) to inhibit monocyte adhesion. Intradermal administration of these LNPs effectively reduced PS formation in both in vivo and in vitro studies. Conclusions This study successfully established a reliable mouse model for PS, highlighting the significant roles of mechanical tension and chronic inflammation in PS formation. We identified Sele as a key therapeutic target and developed Sele-targeted siRNA LNPs, which demonstrated potential as a preventive strategy for PS. These findings provide valuable insights into PS pathogenesis and open new avenues for developing effective treatments for pathological scars. Graphical Abstract
Related Links	https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-024-03003-4.pdf
Ending Page	20
Page Count	20
Starting Page	1
File Format	HTM / HTML
ISSN	14773155
DOI	10.1186/s12951-024-03003-4
Journal	Journal of Nanobiotechnology
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-27
Access Restriction	Open
Subject Keyword	Biotechnology Nanotechnology Molecular Medicine Pathological scar Animal model Mechanical tension RNAi therapy Liposome nanoparticles
Content Type	Text
Resource Type	Article
Subject	Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology
Journal Impact Factor	10.6/2023
5-Year Journal Impact Factor	11.4/2023

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