I-Corps: Magnetic nanoparticles as a magnetic resonance imaging and angiography contrast agent

这个i-Corps项目的更广泛的影响/商业潜力是开发用于生物医学应用的具有更安全轮廓的改进的磁性纳米颗粒。一个特定的市场将是磁共振成像(MRI)的造影剂。目前的基于Gd的造影剂(GBCA)不能用于肾功能不佳的患者，最近的临床研究表明，健康患者的大脑中长期存在Gd的残留。由于Gd是当前GBCA安全问题的来源，一个可能的解决方案是用具有类似对比度增强功能的生物相容铁氧化物取代Gd。传统的铁基磁共振造影剂具有广泛的粒度分布，这导致了不良的副作用和性能的变异性。这里开发的技术能够严格控制颗粒大小分布和物理化学性质，从而提高了试剂的性能和安全性。此外，铁基造影剂可用作外周血管疾病磁共振血管成像(MRA)的造影剂。这项I-Corps项目进一步开发了一种能够明确控制氧化铁纳米颗粒的物理化学性质的技术。这些纳米粒子提供了作为磁共振成像(MRI)和磁共振血管成像(MRA)造影剂的潜力，克服了目前使用的替代品的安全限制。氧化铁纳米颗粒此前已被批准用于临床核磁共振造影剂，但由于性能和安全方面的考虑而停止上市--主要是因为配方的尺寸分布广泛。这里开发的技术使氧化铁纳米颗粒的生产具有高度受控的物理化学性质和低批次之间的可变性，从而产生可重复性的MRI结果。与传统的铁基制剂相比，这种均一配方有望具有更多受控的药代动力学和生物分布特征。

The broader impact/commercial potential of this I-Corps project is the development of improved magnetic nanoparticles with safer profiles for biomedical applications. One specific market would be contrast agents for magnetic resonance imaging (MRI). Current gadolinium-based contrast agents (GBCAs) cannot be administered to patients with poor renal function, and more recent clinical studies indicated long-term residual gadolinium deposition in the brains of healthy patients. As gadolinium is the source of safety concerns for current GBCAs, one possible solution is to replace gadolinium with bio-compatible iron-oxides that offer similar contrast enhancement. Conventional iron-based MRI contrast agents have a broad particle size distribution which results in undesired side effects and performance variability. The technology developed here enables tight control of particle size distribution and physicochemical properties, which improves the agent's performance and safety profile. Moreover, an iron-based contrast agent can be used as a contrast agent for magnetic resonance angiography (MRA) of peripheral vascular diseases.This I-Corps project further develops a technology that enables the explicit control of the physicochemical properties of iron-oxide nanoparticles. These nanoparticles offer potential as magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) contrast agents that overcome the safety limitations of currently used alternatives. Iron-oxide nanoparticles have been previously approved for clinical use as MRI contrast agents but were discontinued from the market due to variable performance and safety concerns - primarily due to formulations with a broad size distribution. The technology developed here enables the production of iron-oxide nanoparticles with highly controlled physiochemical properties and low batch-to-batch variability which yield reproducible MRI results. This homogenous formulation is expected to have more controlled pharmacokinetics and biodistribution profiles compared to conventional iron-based agents.