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整合素 β1 质粒 DNA 负载的阳离子固体脂质纳米粒减轻 IL-1β 诱导的软骨细胞凋亡。

Cationic solid lipid nanoparticles loaded by integrin β1 plasmid DNA attenuates IL-1β-induced apoptosis of chondrocyte.

机构信息

The First Department of Orthopedics, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.

Department of Joint Surgery, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China.

出版信息

Aging (Albany NY). 2020 Nov 27;12(22):22527-22537. doi: 10.18632/aging.103656.

Abstract

Aging-related inflammation is tightly linked with the development of osteoarthritis (OA). As the pro-inflammatory cytokine, IL-1β has been associated with physical dysfunction and frailty. It is still elusive whether and how IL-1β blockade improves the outcome of OA. Here we develop a cationic solid lipid nanoparticles (SLNs) system that effectively mediate non-viral delivery of plasmid DNA (pDNA) into cells. Compared with other DNA transfer technologies including lipofetamin 2000, SLNs-pDNA system is less toxic and exerts identical effectiveness on DNA transfer. Loaded with integrin β1 overexpression pDNA, the SLNs-pDNA mainly localized in cytoplasm and enforced expression of integrin β1 in rat chondrocytes. Moreover, upon exposure to IL-1β stimulation, SLNs-pDNA treatment attenuates the apoptosis rat chondrocytes and augments tissue repair. Our data thus demonstrate that SLNs-pDNA functions as a potential therapeutic nanomedicine in the treatment of osteoarthritis.

摘要

与骨关节炎(OA)的发展密切相关的是与衰老相关的炎症。作为促炎细胞因子,IL-1β与身体机能障碍和虚弱有关。IL-1β 阻断是否以及如何改善 OA 的结果仍然难以捉摸。在这里,我们开发了一种阳离子固体脂质纳米粒(SLN)系统,可有效介导质粒 DNA(pDNA)的非病毒递送至细胞。与包括脂质体 2000 在内的其他 DNA 转移技术相比,SLN-pDNA 系统的毒性更低,对 DNA 转移的效果相同。负载整合素 β1 过表达 pDNA 的 SLN-pDNA 主要定位于细胞质中,并强制表达大鼠软骨细胞中的整合素 β1。此外,在受到 IL-1β 刺激后,SLN-pDNA 处理可减轻大鼠软骨细胞的凋亡并增强组织修复。因此,我们的数据表明,SLN-pDNA 可作为治疗骨关节炎的潜在治疗性纳米医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da99/7746374/c46a7155d7ea/aging-12-103656-g001.jpg

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