Iron Oxide Nanoparticles Enabled Ultrasound-Guided Theranostic Systems

The tumor microenvironment, characterized by higher acidity, hypoxia, and dense cellular structures, plays a pivotal role in cancer progression, therapeutic resistance, and treatment response. Nanoparticle-based contrast agents enable the precise delineation of solid regions within heterogeneous tumors through advanced molecular imaging techniques. Since 1956, ultrasound (US) medical imaging has provided essential anatomical and functional insights about internal organs. More recently, magnetomotive ultrasound (MMUS) has emerged as a promising imaging modality, using a modulated magnetic field to exert force on superparamagnetic iron oxide nanoparticles (SPIONs), inducing motion in the surrounding tissues through mechanical coupling. In parallel, magnetic hyperthermia (MH), which employs localized heating by alternating magnetic fields, has demonstrated significant potential in selectively destroying cancer cells while sparing healthy tissues. This review summarizes the current state of IONP-based contrast agents, with particular emphasis on their use in MH for cancer treatment, as well as their potential in multimodal imaging, including MMUS, and photoacoustic (PA) imaging. The advantages and limitations of IONPs in tumor detection and characterization are discussed, examining the development of surface-functionalized MNPs, and analyzing how material properties and environmental factors affect their diagnostic and therapeutical performance. Finally, strategies for combining MMUS and PA modalities for pre-clinical cancer imaging are proposed.