Journal ArticleSingle-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agentsWei, He; Wiśniowska, Agata; Fan, Jingxuan; Harvey, Peter; Li, Yuanyuan; Wu, Victoria; Hansen, Eric C.; Zhang, Juanye; Kaul, Michael G.; Frey, Abigail M; Adam, Gerhard; Frenkel, Anatoly I.; Bawendi, Moungi G.; Jasanoff, AlanMagnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T 1 -weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood–brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.2021-10-1910319086Proceedings of the National Academy of Sciences118420027-8424https://doi.org/10.1073/pnas.21023401181911592National Science Foundation