Enhanced stability of superparamagnetic iron oxide nanoparticles in biological media using a pH adjusted-BSA adsorption protocol

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biological applications due to their unique properties compared to their bulk counterparts, simplified SPIONs stabilization protocols applicable for a wide spectra of biological media remains a challenging issue. In this work, SPIONs with different surface coatings, tetramethylammonium hydroxide-coated SPIONs (T-SPIONs), and citrate-coated SPIONs (C-SPIONs) were synthesized by a facile, rapid and cost effective microwave-assisted method. C-SPIONs show robust stability in biological media of phosphate buffered saline and Roswell Park Memorial Institute Medium, while destabilize in DMEM. T-SPIONs were found to aggregate rapidly and significantly in all tested media. Then, a modified pH adjusted-BSA adsorption protocol and an addition of excess trisodium citrate dihydrate (Na3Cit) were used to enhance their stability in the media. The BSA adsorption protocol showed great efficiency in stabilizing the dispersed state of both SPIONs in the tested media, while the addition of excess Na3Cit showed limited effect, and it was only applicable for C-SPIONs. The formed BSA layer on SPIONs could be imaged by negative staining TEM, and revealed by Cryo-TEM, FTIR, DLS, and the zeta potential measurements. Results indicated that BSA forms a monolayer of a thickness of about 3 ± 1 nm and BSA interacts with C-SPIONs and T-SPIONs through their coating, rather than by replacing them. This synthetic method and stabilization protocol offer a general methodology to obtain SPIONs with a variety of surfactants, stable in different biological media in few minutes.