Pharmacokinetic Profiling of Unlabeled Magnetic Nanoparticles Using Magnetic Particle Imaging as a Novel Cold Tracer Assay

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Letters Pub Date : 2024-11-26 DOI:10.1021/acs.nanolett.4c03553

Marzieh Salimi, Shreyas Kuddannaya, Jeff W. M. Bulte

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Abstract

We present a magnetic particle imaging (MPI)-based assay for calculating the blood half-life and tissue uptake of magnetic nanoparticles (MNPs) without the need of labeling them. Dual-catheterized rats received 2.0 mg Fe of Synomag^®-D70, Synomag^®-D50, ferucarbotran, and Feraheme^® by femoral vein injection. The MPI signal of blood samples drawn from the femoral artery at various time points was then measured. Synomag^®-D70 exhibited biexponential clearance with half-lives of 3.2 and 31.2 min, Synomag^®-D50 a monoexponential clearance (t_1/2 = 11.4 min), ferucarbotran a biexponential clearance (t_1/2 = 2.4 and 10.8 min), and Feraheme^® a biexponential clearance (t_1/2 = 60.9 and 4.5 min). MPI of perfused tissues showed MNPs primarily localizing in the spleen, liver, and lymph nodes. Spectrophotometric/chemical iron detection proved unreliable due to residual iron from endogenous blood. The MPI assay is a sensitive and specific method for evaluating the pharmacokinetics of existing MNP formulations and those in the pipeline, with exquisite sensitivity for ultrashort half-lives.

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利用磁性粒子成像这种新型冷示踪检测方法分析未标记磁性纳米粒子的药代动力学特征

我们提出了一种基于磁性粒子成像（MPI）的检测方法，用于计算磁性纳米粒子（MNPs）的血液半衰期和组织摄取量，而无需对其进行标记。双导管大鼠通过股静脉注射 2.0 mg Fe 的 Synomag®-D70、Synomag®-D50、ferucarbotran 和 Feraheme®。然后测量不同时间点从股动脉抽取的血液样本的 MPI 信号。Synomag®-D70显示出双指数清除率，半衰期分别为3.2分钟和31.2分钟；Synomag®-D50显示出单指数清除率（t1/2 = 11.4分钟）；ferucarbotran显示出双指数清除率（t1/2 = 2.4分钟和10.8分钟）；Feraheme®显示出双指数清除率（t1/2 = 60.9分钟和4.5分钟）。灌注组织的 MPI 显示，MNPs 主要定位于脾脏、肝脏和淋巴结。由于内源性血液中残留的铁，分光光度法/化学铁检测证明并不可靠。MPI 分析法是评估现有 MNP 制剂和正在开发中的 MNP 制剂药代动力学的一种灵敏而特异的方法，对超短半衰期具有极高的灵敏度。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.