磁共振成像（MRI）已成为临床诊断和预后疗效评估中有价值且广泛应用的检查技术。 MRI造影剂（CA）的引入明显提高了其灵敏度，特别是纳米CA的发展，呈现出更高的对比度增强能力。然而，对其毒性的系统评价仍然有限，阻碍了其在临床上的进一步转化。本文系统评价了一步硬法制备的纳米CA、掺钆介孔碳纳米粒子（Gd-MCNs）的毒性。引入模板法作为模型，临床上采用MRI CA、Magnevist（Gd-DTPA）作为对照。研究并比较了它们的体外血液相容性、细胞毒性、DNA损伤、氧化应激、炎症反应以及体内毒性和磁共振成像行为。实验结果表明，与Gd-DTPA相比，Gd-MCNs对细胞毒性的影响可以忽略不计。红细胞形状、聚集、BSA 结构、巨噬细胞形态和线粒体功能。同时，有限的ROS和炎症细胞因子的产生也说明了Gd-MCN的细胞相容性。对于体内毒性评估，Gd-MCNs 即使在 12 周注射 12 次的情况下也表现出可接受的体内生物安全性。更重要的是，在相同的Gd浓度下，Gd-MCNs比Gd-DTPA表现出更好的肿瘤对比增强效果，这主要来自于其高MRI弛豫率，是Gd-DTPA的近9倍。从不同角度对MRI nano-CA、Gd-MCNs进行毒性评价。以 Gd-DTPA 作为对照，Gd-MCN 似乎是高度生物相容性和安全的纳米颗粒，在 MRI 纳米 CA 的使用中具有广阔的潜力。未来，应该对纳米颗粒的长期遗传毒性和吞咽后的命运进行更多研究。© 2023 张等人。

Magnetic resonance imaging (MRI) has been a valuable and widely used examination technique in clinical diagnosis and prognostic efficacy evaluation. The introduction of MRI contrast agent (CA) improves its sensitivity obviously, particularly with the development of nano-CA, which presents higher contrast enhancement ability. However, systematical evaluation of their toxicity is still limited, hampering their further translation in clinics.In this paper, to systematically evaluate the toxicity of nano-CA, Gd-doped mesoporous carbon nanoparticles (Gd-MCNs) prepared by a one-step hard template method were introduced as a model and clinically used MRI CA, Magnevist (Gd-DTPA) as control. Their in vitro blood compatibility, cellular toxicity, DNA damage, oxidative stress, inflammation response as well as in vivo toxicity and MR imaging behaviors were studied and compared.The experimental results showed that compared with Gd-DTPA, Gd-MCNs displayed negligible influence on the red blood cell shape, aggregation, BSA structure, macrophage morphology and mitochondrial function. Meanwhile, limited ROS and inflammatory cytokine production also illustrated the cellular compatibility of Gd-MCNs. For in vivo toxicity evaluation, Gd-MCNs presented acceptable in vivo biosafety even under 12 times injection for 12 weeks. More importantly, at the same concentration of Gd, Gd-MCNs displayed better contrast enhancement of tumor than Gd-DTPA, mainly coming from its high MRI relaxation rate which is nearly 9 times that of Gd-DTPA.In this paper, we focus on the toxicity evaluation of MRI nano-CA, Gd-MCNs from different angles. With Gd-DTPA as control, Gd-MCNs appeared to be highly biocompatible and safe nanoparticles that possessed promising potentials for the use of MRI nano-CA. In the future, more research on the long-term genotoxicity and the fate of nanoparticles after being swallowed should be performed.© 2023 Zhang et al.