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功能性 Au 纳米颗粒用于特发性肺纤维化治疗中骨髓间充质干细胞的工程设计和长期 CT 成像追踪。

Functional Au nanoparticles for engineering and long-term CT imaging tracking of mesenchymal stem cells in idiopathic pulmonary fibrosis treatment.

机构信息

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China.

出版信息

Biomaterials. 2022 Sep;288:121731. doi: 10.1016/j.biomaterials.2022.121731. Epub 2022 Aug 10.

Abstract

Idiopathic pulmonary fibrosis (IPF) therapy has always been a big and long-standing challenge in clinical practice due to the lack of miraculous medicine. Mesenchymal stem cells (MSCs)-based therapy has recently emerged as a promising candidate for redefining IPF therapy. Enhancing the therapeutic efficacy of MSCs and understanding of their growth, migration and differentiation in harsh lung microenviroments are two keys to improving the stem cell-based IPF treatment. Herein, a non-viral dual-functional nanocarrier is fabricated by a one-pot approach, using protamine sulfate stabilized Au nanoparticles (AuPS), to genetically engineer MSCs for simultaneous IPF treatment and monitoring the biological behavior of the MSCs. AuPS exhibits superior cellular uptake ability, which results in efficient genetic engineering of MSCs to overexpress hepatocyte growth factor for enhanced IPF therapy. In parallel, the intracellular accumulation of AuPS improves the CT imaging contrast of MSCs, allowing visual tracking of the therapeutic engineered MSCs up to 48 days. Overall, this work has described for the first time a novel strategy for enhanced therapeutic efficacy and long-term CT imaging tracking of transplanted MSCs in IPF therapy, providing great prospect for stem cell therapy of lung disease.

摘要

特发性肺纤维化(IPF)的治疗一直是临床实践中的一个重大且长期存在的挑战,因为缺乏神奇的药物。基于间充质干细胞(MSCs)的治疗最近作为重新定义 IPF 治疗的一种有前途的候选方法出现。提高 MSCs 的治疗效果,并了解其在恶劣的肺微环境中的生长、迁移和分化,是改善基于干细胞的 IPF 治疗的两个关键。在此,通过一锅法制备了一种非病毒双功能纳米载体,使用硫酸鱼精蛋白稳定的金纳米颗粒(AuPS)对间充质干细胞进行基因工程改造,用于同时进行 IPF 治疗和监测 MSCs 的生物学行为。AuPS 表现出优异的细胞摄取能力,从而有效地对 MSCs 进行基因工程改造,以过表达肝细胞生长因子,从而增强 IPF 的治疗效果。同时,AuPS 的细胞内积累提高了 MSCs 的 CT 成像对比度,允许对治疗工程化的 MSCs 进行长达 48 天的可视化跟踪。总体而言,这项工作首次描述了一种增强 IPF 治疗中移植的 MSCs 的治疗效果和长期 CT 成像跟踪的新策略,为肺部疾病的干细胞治疗提供了广阔的前景。

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