Factors Ruling the Uptake of Silica Nanoparticles by Mesenchymal Stem Cells: Agglomeration Versus Dispersions, Absence Versus Presence of Serum Proteins

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2015-06, Vol.11 (24), p.2919-2928
• Main Authors: Catalano, Federico, Accomasso, Lisa, Alberto, Gabriele, Gallina, Clara, Raimondo, Stefania, Geuna, Stefano, Giachino, Claudia, Martra, Gianmario
• Format: Article
• Language: English
• Subjects: Adsorption; Agglomerates; Blood Proteins - metabolism; Circular Dichroism; Coronas; Endocytosis; Flow Cytometry; Fluorescent Dyes - chemistry; Humans; Hydrodynamics; Kinetics; mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - ultrastructure; Metal Nanoparticles - chemistry; Nanoparticles; Nanotechnology; Proteins; serum protein adsorption; Serum proteins; silica nanoparticles; Silicon dioxide; Silicon Dioxide - metabolism; Spectrophotometry, Ultraviolet; Stem cells; Temperature; uptake; uptake, mesenchymal stem cells; Uptakes
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201400698

The results of a systematic investigation of the role of serum proteins on the interaction of silica nanoparticles (NP) doped in their bulk with fluorescent molecules (IRIS Dots, 50 nm in size), with human mesenchymal stem cells (hMSCs) are reported. The suspension of IRIS Dots in bare Dulbecco‐modified Eagle's medium results in the formation of large agglomerates (≈1.5 μm, by dynamic light scattering), which become progressively smaller, down to ≈300 nm in size, by progressively increasing the fetal bovine serum (FBS) content of the solutions along the series 1.0%, 2.5%, 6.0%, and 10.0% v/v. Such difference in NP dispersion is maintained in the external cellular microenvironment, as observed by confocal microscopy and transmission electron microscopy. As a consequence of the limited diffusion of proteins in the inter‐NP spaces, the surface of NP agglomerates is coated by a protein corona independently of the agglomerate size/FBS concentration conditions (ζ‐potential and UV circular dichroism measurements). The protein corona appears not to be particularly relevant for the uptake of IRIS Dots by hMSCs, whereas the main role in determining the internalization rate is played by the absence/presence of serum proteins in the extracellular media. The absence of serum proteins in the culture media increases the uptake rate of dye‐doped silica nanoparticles by mesenchymal stem cells. As a consequence, and because of the dispersing action of proteins, bare and large agglomerates of nanoparticles enter the cells more quickly than smaller agglomerates coated with a protein corona.