Exceedingly Small Magnetic Iron Oxide Nanoparticles for T1‐Weighted Magnetic Resonance Imaging and Imaging‐Guided Therapy of Tumors

Abstract Magnetic iron oxide nanoparticles (MIONs) based T 2 ‐weighted magnetic resonance imaging (MRI) contrast agents (CAs) are liver‐specific with good biocompatibility, but have been withdrawn from the market and replaced with Eovist (Gd‐EOB‐DTPA) due to their inherent limitations (e.g., susceptibility to artifacts, high magnetic moment, dark signals, long processing time of T 2 imaging, and long waiting time for patients after administration). Without the disadvantages of Gd‐chelates and MIONs, the recently emerging exceedingly small MIONs (ES‐MIONs) (<5 nm) are promising T 1 CAs for MRI. However, there are rare review articles focusing on ES‐MIONs for T 1 ‐weighted MRI. Herein, the recent progress of ES‐MIONs, including synthesis methods (the current basic synthesis methods and improved methods), surface modifications (artificial polymers, natural polymers, zwitterions, and functional protein), T 1 ‐MRI visual strategies (structural remodeling, reversible self‐assemblies, metal ions doped, T 1 / T 2 dual imaging modes, and PET/MRI strategy), and imaging‐guided cancer therapy (chemotherapy, gene therapy, ferroptosis therapy, photothermal therapy, photodymatic therapy, radiotherapy, immuotherapy, sonodynamic therapy, and multimode therapy), is summarized. The detailed description of synthesis methods and applications of ES‐MIONs in this review is anticipated to attract extensive interest from researchers in different fields and promote their participation in the establishment of ES‐MIONs based nanoplatforms for tumor theranostics.