Biocompatible Nanogold Carrier Coated with Hyaluronic Acid for Efficient Delivery of Plasmid or siRNA to Mesenchymal Stem Cells.

A fluorescein isothiocyanate (FITC)-labeled, hyaluronic acid (HA)-coated nanogld (NP-FITC) was developed to carry plasmid or siRNA into mesenchymal stem cells (MSCs). NP-FITC was characterized by scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectroscopy, and Fourier transform infrared (FTIR) spectrophotometry. Nontoxicity of NP-FITC in both normal cells and cancer cells was confirmed by the MTT assay. The cellular uptake of NP-FITC at different time points (30 min, 2 h, and 24 h) was verified using an immunofluorescence assay. The delivery efficiency of plasmid was tested on the delivery of superoxide dismutase-1 (SOD-1) plasmid, where the protein expression of SOD-1 was analyzed by Western blots. In addition, the delivery efficiency of siRNA was tested using CXCR4 siRNA. Besides, the siRNA delivery by NP-FITC was employed to elucidate the molecular mechanism associated with the effect of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1). The biological function of MSCs delivered with chemokine (C-X-C motif) receptor 4 (CXCR4) siRNA was examined using ELISA, gelatin zymography, and a migration assay. Finally, we evaluated the tissue distribution of NP-FITC after the direct injection in the retro orbital sinus of mice or after injection of NP-FITC internalized MSCs through the tail vein of mice. The data provided essential information for NP-FITC as a plasmid or siRNA carrier.