4.7 Article

Therapeutic Applications of Mesenchymal Stem Cell Loaded with Gold Nanoparticles for Regenerative Medicine

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PHARMACEUTICS
卷 15, 期 5, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics15051385

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gold nanoparticle; mesenchymal stem cell; biological performance; nanodrug delivery

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This study investigated the biocompatibility, biological performances, and cell uptake efficiency of AuNP in Wharton's jelly mesenchymal stem cells and a rat model. Various concentrations of AuNP were prepared and characterized. In vitro examinations showed that treatment with 1.25 and 2.5 ppm AuNP improved viability, CXCR4 expression, migration distance, and reduced apoptotic-related protein expression in Wharton's jelly MSCs. AuNP-Col was taken up by cells via clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway. In vivo examinations demonstrated that 2.5 ppm AuNP attenuated foreign body responses and had better retention efficacy in tissue integrity. Overall, AuNP shows promise as a biosafe nanodrug delivery system for regenerative medicine with Wharton's jelly MSCs.
In the present study, the various concentrations of AuNP (1.25, 2.5, 5, 10 ppm) were prepared to investigate the biocompatibility, biological performances and cell uptake efficiency via Wharton's jelly mesenchymal stem cells and rat model. The pure AuNP, AuNP combined with Col (AuNP-Col) and FITC conjugated AuNP-Col (AuNP-Col-FITC) were characterized by Ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic Light Scattering (DLS) assays. For in vitro examinations, we explored whether the Wharton's jelly MSCs had better viability, higher CXCR4 expression, greater migration distance and lower apoptotic-related proteins expression with AuNP 1.25 and 2.5 ppm treatments. Furthermore, we considered whether the treatments of 1.25 and 2.5 ppm AuNP could induce the CXCR4 knocked down Wharton's jelly MSCs to express CXCR4 and reduce the expression level of apoptotic proteins. We also treated the Wharton's jelly MSCs with AuNP-Col to investigate the intracellular uptake mechanisms. The evidence demonstrated the cells uptake AuNP-Col through clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway with good stability inside the cells to avoid lysosomal degradation as well as better uptake efficiency. Additionally, the results from in vivo examinations elucidated the 2.5 ppm of AuNP attenuated foreign body responses and had better retention efficacy with tissue integrity in animal model. In conclusion, the evidence demonstrates that AuNP shows promise as a biosafe nanodrug delivery system for development of regenerative medicine coupled with Wharton's jelly MSCs.

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