High sensitivity at ultra-high field (UHF) and sufficient potential to penetrate the brain are the most desirable characteristics in the development of contrast agents (CAs) for magnetic resonance imaging (MRI). However, incorporating such qualities into a single nanocarrier is challenging. Herein, we report a new strategy for a highly brain-permeable MR CA with high sensitivity at UHF by loading dysprosium chelates (DyL) in apoferritin cavities (Apo-DyL). We also design the chelate ligand structure to increase DyL loading capacity within the apoferritin cavity. Using the intracerebroventricular (ICV) injection approach as a new delivery route for Apo-DyL, we demonstrate that apoferritin loaded with DyL can penetrate the brain–ventricular barrier and diffuse into the brain. This brain-permeable capability is unique to Apo-DyL, compared with other types of nanoparticles used in MRI. Apo-DyL also shows significant increase in MR sensitivity of DyL at UHF. Furthermore, based on brain tumor imaging at UHF, Apo-DyL can significantly enhance the tumor for a lower dose of the CA than the previously reported Gd- or Mn-loaded apoferritin nanoplatform. Therefore, Apo-DyL can be a novel nanoplatform that is a highly sensitive and versatile MR CA for UHF brain imaging.

在用于磁共振成像（MRI）的造影剂（CA）的开发中，超高场（UHF）的高灵敏度和足够的潜力可以穿透大脑是最理想的特性。然而，将这样的品质结合到单个纳米载体中是具有挑战性的。在这里，我们报告了一种新的策略，通过在A铁蛋白腔（Apo-DyL）中加载loading螯合物（DyL），在UHF上具有高敏感性的高脑通透性MRCA。我们还设计了螯合配体结构，以增加载铁蛋白腔内DyL的负载能力。使用脑室内注射（ICV）作为Apo-DyL的新递送途径，我们证明载有DyL的载铁蛋白可以穿透脑室屏障并扩散到大脑中。这种透脑能力是Apo-DyL独有的，与MRI中使用的其他类型的纳米粒子相比。Apo-DyL在超高频下也显示DyL的MR敏感性显着提高。此外，基于超高频下的脑肿瘤成像，与以前报道的载有Gd或Mn的载铁蛋白纳米平台相比，Apo-DyL可以显着增强肿瘤并降低其CA剂量。因此，Apo-DyL可以是一种新型的纳米平台，它是用于UHF脑成像的高度灵敏且通用的MRCA。