Recent advances on stimuli-responsive macromolecular magnetic resonance imaging (MRI) contrast agents

Magnetic resonance imaging (MRI) has been extensively used in clinical diagnosis and currently over 30% MRI runs are performed in the presence of contrast agents. However, commercially available contrast agents originated from small molecules typically exhibit relatively low relaxivities and insufficient circulation time. Therefore, there is a long pursuit to develop new contrast agents with high relaxivities to discriminate pathological tissues from normal ones. Compared with small molecule MRI contrast agents, the incorporation of small molecule contrast agents into macromolecular scaffolds allows for constructing macromolecular MRI contrast agents, remarkably elevating the relaxivities due in part to increased rotational correlation time (τ_R). Moreover, if the macromolecular scaffolds are responsive to external stimuli, the MRI signals could be selectively switched on at the desired sites (e.g., pathological tissues), further intensifying the imaging contrast. In this feature article, we outline the recent achievements in the fabrication of stimuli-responsive macromolecular MRI contrast agents. Specifically, macromolecular contrast agents being responsive to acidic pH, redox potentials, and other stimuli including photoirradiation, pathogens, and salt concentration are discussed. These smart contrast agents could affect either longitudinal (T₁) or transverse (T₂) relaxation times of water protons or other nuclei (e.g., ¹⁹F), exhibiting enhanced signals in pathological tissues yet suppressed signals in normal ones and displaying promising potentials in in vitro and in vivo MRI applications.