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聚合纳米颗粒使mRNA传染及其转化在椎间盘和人类关节细胞中,除了M1巨细胞外

Katrin Agnes Muenzebrock¹, Fiona Y W Ho¹, Adriano P Pontes²

¹Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

|April 27, 2024

概括

聚合物纳米颗粒有效地将mRNA传递给人类关节和椎间盘细胞,为治疗骨关节炎和椎间盘退化提供了潜力. 这种方法对疾病修饰有希望,不包括巨细胞.

科学领域:

生物材料科学生物材料科学
再生医学是一种再生医学.
分子疗法分子疗法

背景情况:

脊椎间盘退化 (IVDD) 和骨关节炎 (OA) 引起的慢性腰部疼痛很普遍,缺乏疾病修饰性治疗.
传递信使RNA (mRNA) 提供了一个潜在的策略来调节炎症并促进关节和盘组织的再生.

研究的目的:

研究基于聚胺胺的聚合物纳米颗粒在将mRNA输入人类关节和椎间盘细胞中的有效性.
评估这些纳米颗粒在各种相关细胞类型中的安全性和转染效率.

主要方法:

培养的人类OA冠状细胞,核脉 (NP) 细胞,环纤维细胞 (AF) 细胞,纤维细胞样同胞细胞 (FLS) 和M1-样巨细胞.
使用未涂层或PGA-PEG涂层的聚胺胺胺) 纳米颗粒,用EGFP编码mRNA转染细胞.
分析了细胞活力,转染效率和纳米粒子内部化.

主要成果:

聚合物纳米颗粒证明了mRNA传递和EGFP表达在NP细胞,AF细胞,OA冠状细胞和FLS中,对细胞活力的影响最小.
巨细胞显示纳米粒子内部化,但没有可检测的EGFP表达,观察到剂量依赖的活力下降.
无论是未涂层的纳米颗粒还是PGA-PEG涂层的纳米颗粒,都有效地将mRNA传递到目标细胞.

结论:

基于多胺胺的纳米颗粒是一种可行的系统,可以将mRNA输入人类关节和椎间盘细胞.
这项技术有可能在骨关节炎和椎间盘退行症中获得未来的治疗应用,并特别考虑巨细胞群.

关键词:

慢性下背部疼痛慢性下背部疼痛提供mRNA的交付.纳米医药是一种纳米医药.骨关节炎是一种关节炎.

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