Immune compatible cystine-functionalized superparamagnetic iron oxide nanoparticles as vascular contrast agents in ultrasonography

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively investigated for many biomedical applications. A good quality functionalization that combines imaging goals with a high-level of biocompatibility remains one of the challenges for particle translation into medical practice. Here, we focus on a new functionalization of SPIONs with cystine (Cy-SPIONs). Cystine is able to make SPIONs stable and dispersible in water and in culture cell media. New insights are provided into the biological and immune effects of Cy-SPIONs with a wide variety of standard and molecular assays to evaluate cytotoxicity, cell activation, cytokine release and the expression of 84 genes related to immune responses. A good immune biocompatibility of Cy-SPIONs on primary immune cells was found. The great potential of Cy-SPIONs for further in vivo studies and as contrast agents for magnetic resonance imaging (MRI) is highlighted. In addition, we also exploited ultrasonography, since it is a safer, less expensive and common imaging technology. The good echogenic properties of Cy-SPIONs in water and in whole blood are shown, both in vitro and in a phantom vein for bloodstream simulations. Our results open up a new scenario for future applications of cystine-functionalized SPIONs as immune-compatible ultrasound and MRI contrast agents.