TEMPO-Conjugated Gold Nanoparticles for Reactive Oxygen Species Scavenging and Regulation of Stem Cell Differentiation
TEMPO-Conjugated Gold Nanoparticles for Reactive Oxygen Species Scavenging and Regulation of Stem Cell Differentiation
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DOI：
10.1021/acsami.7b12486
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发表时间：
2017-10-18
影响因子：
9.5
通讯作者：
Chen, Guoping
中科院分区：
文献类型：
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作者：
Li, Jingchao;Zhang, Jing;Chen, Guoping
控制人骨髓间充质干细胞（hMSCs）的分化在再生医学中显示出巨大的潜力。由于过量产生的活性氧（reactive oxygen species，ROS）对hMSCs的分化和功能有明显的抑制作用，因此，开发一种有效的清除ROS和调控干细胞分化的策略是非常必要的。在这项研究中，金纳米粒子（Au NPs）的平均尺寸为40 nm的共轭与2，2，6，6-四甲基哌啶-N-氧基（克里思），赋予他们与ROS清除能力，同时保持Au NPs的有益效果。将TEMPO标记的Au NPs（Au-PEG-克里思NPs）用于hMSCs的培养，以研究其对hMSCs的ROS清除、增殖以及成骨和成脂分化的影响。Au-PEG-克里思NPs对hMSCs的细胞活力和增殖的影响可以忽略不计，并且由于其优异的细胞摄取，可以有效地降低H2 O2暴露条件下hMSCs的ROS水平。与表面克里思修饰的纳米颗粒（Au-mPEG NPs）相似，Au-PEG-克里思NPs能促进hMSCs的成骨分化，但能抑制hMSCs的成脂分化。结果表明，TEMPO标记的Au NPs对细胞内产生的活性氧有较强的清除能力，并保持了Au NPs对hMSCs成骨分化的促进作用，而不受游离克里思的抑制。本研究为干细胞移植和再生医学中清除活性氧控制干细胞分化提供了一个有前途的策略。
Controlling the differentiation of human mesenchymal stem cells (hMSCs) shows a great potential in regenerative medicine. Because overproduced reactive oxygen species (ROS) have an obvious inhibitory effect on the differentiation and functions of hMSCs, it is highly desirable to develop an effective strategy for ROS scavenging and stem cell differentiation controlling. In this study, gold nanoparticles (Au NPs) with an average size of 40 nm were conjugated with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to endow them with ROS-scavenging capacity while holding the beneficial effect of Au NPs. The TEMPO-conjugated Au NPs (Au-PEG-TEMPO NPs) were used for the culture of hMSCs to investigate their effect on ROS scavenging, proliferation, and osteogenic and adipogenic differentiation of hMSCs. The Au-PEG-TEMPO NPs had a negligible influence on cell viability and proliferation of hMSCs and could effectively reduce the ROS level of hMSCs under H2O2-exposed conditions because of their excellent cellular uptake. Similar to the counterparts without surface TEMPO modification (Au-mPEG NPs), the Au-PEG-TEMPO NPs could promote the osteogenic differentiation of hMSCs, whereas they could inhibit the adipogenic differentiation of hMSCs. The results indicated that the TEMPO-conjugated Au NPs had high scavenging capacity for overproduced ROS and maintained the promotive effect of Au NPs on osteogenic differentiation of hMSCs without the inhibitory effect of free TEMPO. This study offers a promising strategy for ROS scavenging to control stem cell differentiation in stem cell transplantation and regenerative medicine.