Efficacy and Durability in Direct Labeling of Mesenchymal Stem Cells Using Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Organosilica, Dextran, and PEG Coatings

Abstract

We herein report a comparative study of mesenchymal stem cell (MSC) labeling using spherical superparamagnetic iron oxide (SPIO) nanoparticles containing different coatings, namely, organosilica, dextran, and poly(ethylene glycol) (PEG). These nanomaterials possess a similar SPIO core size of 6–7 nm. Together with their coatings, the overall sizes are 10–15 nm for all SPIO@SiO2, SPIO@dextran, and SPIO@PEG nanoparticles. These nanoparticles were investigated for their efficacies to be uptaken by rabbit bone marrow-derived MSCs without any transfecting agent. Experimentally, both SPIO@SiO2 and SPIO@PEG nanoparticles could be successfully uptaken by MSCs while the SPIO@dextran nanoparticles demonstrated limited labeling efficiency. The labeling durability of SPIO@SiO2 and SPIO@PEG nanoparticles in MSCs after three weeks of culture were compared by Prussian blue staining tests. SPIO@SiO2 nanoparticles demonstrated more blue staining than SPIO@PEG nanoparticles, rendering them better materials for MSCs labeling by direct uptake when durable intracellullar retention of SPIO is desired.

Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking

“…The result demonstrated that six-arm amine-functionalized PEG (6(PEG-NH 2 )) was a superior dispersion agent for the monodispersed SPIONs. However, PEG is well known for its “stealthy” effect and not favorable for most cells to uptake SPIONs with PEG shell protection 130. Therefore, SPIONP-6PEG-NH 2 was modified by hyaluronic acid (HA), a targeting moiety, for stem cell uptake.…”

“…Silica (SiO 2 ) with good biocompatibility is demonstrated to serve as a good coating material for magnetic NPs 76, 78, 130, 135. Silica coating on the surface of SPIONs prevents their aggregation in aqueous solution, improves their chemical and biological stability, and provides better biocompatibility 76.…”

Increased Efficacies in Magnetofection and Gene Delivery to Hepatocellular Carcinoma Cells with Ternary Organic–Inorganic Hybrid Nanocomposites

“…Superparamagnetic iron oxide nanoparticles (Fe 3 O 4 -(OH) n NPs) with an average diameter of 8-10 nm were synthesized according to literature procedures. [22][23][24] These Fe 3 O 4 -(OH) n NPs were first treated with an excess of succinic anhydride in DMF at room temperature for 24 h under gentle shaking, followed by repeated separation with a magnet and washing with DMF. Subsequently, the black residue (nanoparticles) was washed with anhydrous THF and redispersed in anhydrous THF by using ultrasound (Elma Tl-H-5 instrument, 5 min, 35 kHz).…”

Preparation and Characterization of Ferrofluid Stabilized with Biocompatible Chitosan and Dextran Sulfate Hybrid Biopolymer as a Potential Magnetic Resonance Imaging (MRI) T2 Contrast Agent

“…In the field of clinical regenerative medicine, iron oxide nanoparticles have been used as a tool for magnetic resonance image tracking of stem cells and have also been recently reviewed [3]. A crucial aspect during the preparation of the SPIONs is to control their size distribution and prevent aggregation [4] by employing macromolecules as coating agents, especially in polysaccharides polymers [5,6,7,8,9]. For in vivo MRI contrast agent applications, colloidally monodispersed magnetic nanoparticles, which are known as a ferrofluid, that have a high magnetic relaxivity (r2/r1) ratio and are stable at neutral pH are highly desired [10].…”

“…, the molar fraction of acetylated residues in the polymer, which is responsible for both the charge density of the polymer and the balance between the hydrophilic and hydrophobic interactions. In the field of biopolymers, chitosan is well known for its outstanding biological properties, including biodegradability and biocompatibility, which allow for its wide applications [5,9,11,12], including tissue engineering [13,14,15] and drug release [16,17]. Also, the primary amines on chitosan are particularly interesting in metal nanoparticle synthesis due to their interaction with metal ions and metal oxide nanoparticles.…”