J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
Department of Chemical Engineering, University of Florida, Gainesville, FL, USA.
J Control Release. 2023 Apr;356:347-359. doi: 10.1016/j.jconrel.2023.02.038. Epub 2023 Mar 10.
Nanoparticles are a promising approach for improving intra-articular drug delivery and tissue targeting. However, techniques to non-invasively track and quantify their concentration in vivo are limited, resulting in an inadequate understanding of their retention, clearance, and biodistribution in the joint. Currently, fluorescence imaging is often used to track nanoparticle fate in animal models; however, this approach has limitations that impede long-term quantitative assessment of nanoparticles over time. The goal of this work was to evaluate an emerging imaging modality, magnetic particle imaging (MPI), for intra-articular tracking of nanoparticles. MPI provides 3D visualization and depth-independent quantification of superparamagnetic iron oxide nanoparticle (SPION) tracers. Here, we developed and characterized a polymer-based magnetic nanoparticle system incorporated with SPION tracers and cartilage targeting properties. MPI was then used to longitudinally assess nanoparticle fate after intra-articular injection. Magnetic nanoparticles were injected into the joints of healthy mice, and evaluated for nanoparticle retention, biodistribution, and clearance over 6 weeks using MPI. In parallel, the fate of fluorescently tagged nanoparticles was tracked using in vivo fluorescence imaging. The study was concluded at day 42, and MPI and fluorescence imaging demonstrated different profiles in nanoparticle retention and clearance from the joint. MPI signal was persistent over the study duration, suggesting NP retention of at least 42 days, much longer than the 14 days observed based on fluorescence signal. These data suggest that the type of tracer - SPIONs or fluorophores - and modality of imaging can affect interpretation of nanoparticle fate in the joint. Given that understanding particle fate over time is paramount for attaining insights about therapeutic profiles in vivo, our data suggest MPI may yield a quantitative and robust method to non-invasively track nanoparticles following intra-articular injection on an extended timeline.
纳米颗粒是一种有前途的方法，可以改善关节内药物输送和组织靶向。然而，非侵入性地跟踪和量化其在体内浓度的技术有限，导致对其在关节中的保留、清除和生物分布的理解不足。目前，荧光成像常用于跟踪动物模型中纳米颗粒的命运；然而，这种方法存在限制，阻碍了随着时间的推移对纳米颗粒进行长期定量评估。这项工作的目的是评估一种新兴的成像方式，即磁粒子成像 (MPI)，用于关节内跟踪纳米颗粒。MPI 提供超顺磁氧化铁纳米颗粒 (SPION) 示踪剂的 3D 可视化和深度独立定量。在这里，我们开发并表征了一种聚合物基磁性纳米颗粒系统，该系统结合了 SPION 示踪剂和软骨靶向特性。然后，我们使用 MPI 纵向评估关节内注射后纳米颗粒的命运。将磁性纳米颗粒注入健康小鼠的关节中，并用 MPI 在 6 周内评估纳米颗粒的保留、生物分布和清除。同时，使用体内荧光成像跟踪荧光标记纳米颗粒的命运。研究在第 42 天结束，MPI 和荧光成像显示了纳米颗粒在关节中的保留和清除的不同特征。MPI 信号在整个研究过程中持续存在，表明 NP 保留至少 42 天，比荧光信号观察到的 14 天长得多。这些数据表明，示踪剂的类型（SPION 或荧光团）和成像方式会影响对关节中纳米颗粒命运的解释。考虑到随着时间的推移了解颗粒命运对于获得体内治疗特征的见解至关重要，我们的数据表明，MPI 可能会提供一种定量且强大的方法，用于在延长的时间内非侵入性地跟踪关节内注射后的纳米颗粒。
