Stimulus‐Responsive Nanoparticle Magnetic Resonance Imaging Contrast Agents: Design Considerations and Applications

Abstract Magnetic resonance imaging (MRI) has been widely used for disease diagnosis because it can noninvasively obtain anatomical details of various diseases through accurate contrast between soft tissues. Over one‐third of MRI examinations are performed with the assistance of contrast agents. Traditional contrast agents typically display an unchanging signal, thus exhibiting relatively low sensitivity and poor specificity. Currently, advances in stimulus‐responsive contrast agents which can alter the relaxation signal in response to a specific change in their surrounding environment provide new opportunities to overcome such limitation. The signal changes based on stimulus also reflects the physiological and pathological conditions of the site of interests. In this review, how to design stimulus‐responsive nanoparticle MRI contrast agents from the perspective of theory and surface design is comprehensively discussed. Key structural features including size, clusters, shell features, and surface properties are used for tuning the T 1 and T 2 relaxation properties. The reversible or non‐reversible signal changes highlight the contrast agents have undergone structural changes based on certain stimulus, as an indication for disease diagnosis or therapeutic efficacy.