Magnetic 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.

磁性纳米粒子是 MRI 的强大造影剂，通常每个粒子都会产生特别强烈的信号变化。然而，利用这些效应来探测组织中的细胞和分子水平现象可能会受到大尺寸典型纳米颗粒造影剂的阻碍。为了解决这一限制，我们引入了单纳米氧化铁 (SNIO) 颗粒，该颗粒表现出超顺磁性以及与小型、高扩散性显像剂相当的流体动力学直径。这些粒子有效地使T ₁中的信号变亮加权 MRI，产生的每分子纵向松弛增强比传统的钆造影剂高 10 倍以上。我们表明 SNIO 在注入脑实质或脑脊液后有效地渗透生物组织。我们还证明 SNIO 在超声诱导的血脑屏障破坏后很容易进入大脑，模仿钆剂的性能，并为未来的生物医学应用提供基础。因此，这些结果展示了一个 MRI 探针开发平台，该平台结合了小分子显像剂的优势和纳米材料的效力。