Light‐Addressable Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Enhanced and Dynamic Magnetic Resonance Imaging of Arthritis

Design of novel nanoplatforms with single imaging elements for dynamic and enhanced T1/T2-weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light-addressable ultrasmall Fe3O4 nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic T1/T2-weighted MR imaging of inflammatory arthritis is reported. Citric acid-stabilized ultrasmall Fe3O4 NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light-addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer. The formed ultrasmall Fe3O4-PEG-(DA)-FA NPs are cytocompatible, display FA-mediated targeting specificity to arthritis-associated macrophage cells, and can form NCs upon laser irradiation to have tunable r1 and r2 relaxivities by varying the laser irradiation duration. With these properties owned, the designed Fe3O4-PEG-(DA)-FA NPs can be used for T1-weighted MR imaging of arthritis without lasers and enhanced dual-mode T1/T2-weighted MR imaging of arthritis under laser irradiation due to the formation of NCs that have extended accumulation within the arthritis region and limited intravasation back to the blood circulation. The designed light-addressable Fe3O4-PEG-(DA)-FA NPs may be used as a promising platform for dynamic and precision T1/T2-weighted MR imaging of other diseases.