Ultrasmall Mixed Eu-Gd Oxide Nanoparticles for Multimodal Fluorescence and Magnetic Resonance Imaging of Passive Accumulation and Retention in TBI
Ultrasmall Mixed Eu-Gd Oxide Nanoparticles for Multimodal Fluorescence and Magnetic Resonance Imaging of Passive Accumulation and Retention in TBI
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DOI：
10.1021/acsomega.0c01890
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发表时间：
2020-07-07
期刊：
影响因子：
4.1
通讯作者：
Kievit, Forrest M.
中科院分区：
文献类型：
--
作者：
Bony, Badrul Alam;Miller, Hunter A.;Kievit, Forrest M.
创伤性脑损伤（TBI）是全世界死亡和残疾的主要原因。 TBI 会对所有年龄段的幸存者的生活质量产生长期影响。然而，目前还没有批准的治疗方法可以改善 TBI 后的预后，部分原因是治疗药物输送到大脑的效果不佳。因此，迫切需要开发更有效的递送策略，以增加受伤大脑中潜在有效治疗的积累和保留。最近的研究表明，纳米颗粒（NP）可能为定点递送提供一种有前景的方法。然而，对促进大脑积累和保留的特定 NP 特性的详细了解仍在发展中。多模态成像在理解物理化学特性方面发挥着至关重要的作用，这些特性在高空间频率（例如荧光成像）和时间频率（例如磁共振成像、MRI）下启动大脑中纳米颗粒的摄取和积累。然而，目前TBI中使用的许多NP系统仅在单一成像模态中提供对比度，限制了可以获得的成像数据，而那些提供多模态成像能力的NP系统具有复杂的多步骤合成方法。因此，这项工作的目标是开发一种制造简单、能够进行多模态成像的超小型纳米粒子。在这里，我们描述了 TBI 受控皮质冲击小鼠模型中聚乙二醇 (PEG) 包被的铕钆 (Eu-Gd) 混合磁性纳米粒子 (MNP) 的开发、表征、积累和保留。我们发现这些纳米颗粒具有 2 nm 的超小核心尺寸和 13.5 nm 的小流体动力学尺寸，可以在荧光和 MR 成像模式中检测到，并快速积累并保留在受损的脑实质中。这些 NP 应该允许进一步测试 NP 的理化特性，以促进 TBI 和其他疾病模型中的积累和保留。
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBI can have a long-term impact on the quality of life for survivors of all ages. However, there remains no approved treatment that improves outcomes following TBI, which is partially due to poor delivery of therapies into the brain. Therefore, there is a significant unmet need to develop more effective delivery strategies that increase the accumulation and retention of potentially efficacious treatments in the injured brain. Recent work has revealed that nanoparticles (NPs) may offer a promising approach for site-specific delivery; however, a detailed understanding of the specific NP properties that promote brain accumulation and retention are still being developed. Multimodal imaging plays a vital role in the understanding of physicochemical properties that initiate the uptake and accumulation of NPs in the brain at both high spatial (e.g., fluorescence imaging) and temporal (e.g., magnetic resonance imaging, MRI) frequency. However, many NP systems that are currently used in TBI only provide contrast in a single imaging modality limiting the imaging data that can be obtained, and those that offer multimodal imaging capabilities have complicated multistep synthesis methods. Therefore, the goal of this work was to develop an ultrasmall NP with simple fabrication capable of multimodal imaging. Here, we describe the development, characterization, accumulation, and retention of poly(ethylene glycol) (PEG)-coated europium-gadolinium (Eu-Gd) mixed magnetic NPs (MNPs) in a controlled cortical impact mouse model of TBI. We find that these NPs having an ultrasmall core size of 2 nm and a small hydrodynamic size of 13.5 nm can be detected in both fluorescence and MR imaging modalities and rapidly accumulate and are retained in injured brain parenchyma. These NPs should allow for further testing of NP physicochemical properties that promote accumulation and retention in TBI and other disease models.