Chitosan-Coated Superparamagnetic Fe₃O₄ Nanoparticles for Magnetic Resonance Imaging, Magnetic Hyperthermia, and Drug Delivery

Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for biomedical applications as multipurpose magnetic resonance imaging (MRI) contrast agents, and some systems have already been approved by The United States Food and Drug Administration for clinical use. Superparamagnetic behavior, high magnetic saturation, and fast synthesis are the major advantages of these nanomaterials. Polymer coatings are often used to prevent cluster formation and to improve biocompatibility of nanoparticles. In this work, we propose to use chitosan (CS) coatings as a means to tune the biocompatibility and magnetic properties of the SPIONs. For this purpose, magnetite (Fe3O4) SPIONs with various CS coatings were synthesized. CS with identical degree of polymerization (DPw = 450) but different degrees of acetylation (DA of 1, 14, and 34%) were employed to tune the hydrophilic properties of the SPIONs’ coatings. A highly crystalline magnetite phase with a superparamagnetic behavior was evidenced for all the studied nanoparticles, whose average sizes varied between 5 and 10 nm. Adjusting the preparation process enabled us to control precisely the amount of coating on the SPIONs. Such coatings significantly impacted their magnetic properties, which were found to decrease with the quantity of CS and also with its DA. Interestingly, cytocompatibility was enhanced by the presence of the CS coating so that all CS-coated SPIONs studied were found to be nontoxic, regardless of the amount of coating . This trade-off approach suggests that optimal SPIONs systems would consist of a magnetite core, coated with a low amount of low-DA CS. Finally, the multimodal features of the SPIONs were evidenced by performing magnetic hyperthermia and MRI measurements. Despite significant differences, for all the CS-coated SPIONs, the magnetic properties remained strong enough to envision their use in various biomedical applications such as magnetic hyperthermia, MRI contrast agents, magnetic field-assisted drug delivery, and as platforms for further biological functionalization.