TEMPO-Conjugated Gold Nanoparticles for Reactive Oxygen Species Scavenging and Regulation of Stem Cell Differentiation

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.