Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging.
Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging.
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DOI：
10.2147/ijn.s138108
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发表时间：
2017
影响因子：
8
通讯作者：
Cicha I
中科院分区：
文献类型：
--
作者：
Unterweger H;Janko C;Schwarz M;Dézsi L;Urbanics R;Matuszak J;Őrfi E;Fülöp T;Bäuerle T;Szebeni J;Journé C;Boccaccini AR;Alexiou C;Lyer S;Cicha I
基于氧化铁的造影剂已在临床上用于淋巴结、肝脏、肠道和心血管系统的磁共振成像 (MRI)。超顺磁性氧化铁纳米颗粒（SPION）作为 MRI 造影剂具有很高的潜力，但目前还没有静脉注射含氧化铁的试剂被批准用于临床成像。我们工作的目的是分析新型葡聚糖涂层 SPION (SPIONdex) 的血液相容性和免疫安全性，并通过超高场 MRI 表征这些纳米颗粒。在体外和离体研究了与纳米颗粒血液相容性和免疫安全性相关的关键参数。为了解决与可注射纳米颗粒剂过敏反应相关的问题，我们分析了猪模型静脉注射 SPIONdex 后的补体激活相关假性过敏 (CARPA)。此外，还研究了 SPIONdex 的尺寸可调性以及尺寸减小对其生物相容性的影响。在体外，SPIONdex 不会引起溶血、补体或血小板活化、血浆凝固或白细胞促凝血活性，并且对内皮细胞活力或内皮-单核细胞相互作用没有相关影响。此外，即使在猪体内静脉注射 5 mg Fe/kg，SPIONdex 也不会诱导 CARPA。小鼠服用 SPIONdex 后，15 分钟后观察到肝脏信号强度降低，24 小时后仍可检测到。此外，通过改变合成参数，实现了粒径<30 nm的减小，而不影响其血液和生物相容性。我们的研究结果表明，由于 SPIONdex 颗粒具有出色的生物相容性、静脉注射的安全性和尺寸可调性，因此可能是新一代 MRI 造影剂的合适候选者。
Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial–monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.