MRI Directed Magnevist Effective to Study Toxicity of Gd-Doped Mesoporous Carbon Nanoparticles in Mice Model

Chun Zhang; Changzhou Shi; Pengzhao Chang; Shuang Bian; Bangbang Li; Jingjing Li; Pingfu Hou

doi:10.2147/IJN.S433213

MRI Directed Magnevist Effective to Study Toxicity of Gd-Doped Mesoporous Carbon Nanoparticles in Mice Model

Int J Nanomedicine. 2023 Oct 27:18:6119-6136. doi: 10.2147/IJN.S433213. eCollection 2023.

Authors

Chun Zhang^{1

2}, Changzhou Shi¹, Pengzhao Chang¹, Shuang Bian^{1

2}, Bangbang Li¹, Jingjing Li^{1

2}, Pingfu Hou^{2

3}

Affiliations

¹ School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
² Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People's Republic of China.
³ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: MRI; cytotoxicity; immunotoxicity; nano-contrast agent; tissue toxicity.

MeSH terms

Animals
Carbon
Contrast Media / chemistry
Contrast Media / toxicity
Gadolinium DTPA* / chemistry
Magnetic Resonance Imaging / methods
Mice
Nanoparticles* / chemistry
Nanoparticles* / toxicity

Substances

Gadolinium DTPA
Contrast Media
Carbon