Iron oxide-loaded nanotheranostics: major obstacles to in vivo studies and clinical translation.

A major issue in current cancer therapies is the lack of selectivity, which leads to damage in healthy tissues. Therefore, researchers have focused on numerous innovative targeting strategies to address this problem with the goal of increasing selectivity to avoid or minimize accumulation in healthy tissues. These strategies include (i) passive targeting, (ii) active targeting and (iii) stimuli-mediated targeting. Moreover, due to the high intra- and inter-variability found in tumors, nanotheranostics, which is the combination of a therapeutic and an imaging agent in a single vector, have emerged as indispensable tools for personalized therapy. Superparamagnetic iron oxide (SPIO) are MRI contrast agents that produce predominant T2 relaxation effects with excellent sensitivity compared with other MRI agents. Therefore, they have received increased interest in the field of theranostics during the past decade. However, few studies have been successfully conducted in vivo. This review aims to provide an overview of the targeted SPIO-based nanotheranostics recently used in pre-clinical studies and the major obstacles to in vivo studies and clinical translation. In the first section, we discuss personalized therapy as a biomedical application of theranostics. Then, we summarize the different imaging agents that have been used for theranostic purposes, with a focus on SPIO. In the third section, we detail recent advances in targeted SPIO-based nanotheranostics that have been used in pre-clinical studies. In the final sections, we discuss the limitations for in vivo studies, clinical translation and the clinical perspectives of SPIO-based nanotheranostics.