Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance

Kun Liu; Liang Dong; Yunjun Xu; Xu Yan; Fei Li; Yang Lu; Wei Tao; Huangyong Peng; Yadong Wu; Yang Su; Daishun Ling; Tao He; Haisheng Qian; Shu-Hong Yu

doi:10.1016/j.biomaterials.2017.12.023

Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance

Biomaterials. 2018 Mar:158:74-85. doi: 10.1016/j.biomaterials.2017.12.023. Epub 2017 Dec 28.

Authors

Kun Liu¹, Liang Dong², Yunjun Xu³, Xu Yan¹, Fei Li¹, Yang Lu⁴, Wei Tao¹, Huangyong Peng¹, Yadong Wu¹, Yang Su¹, Daishun Ling⁵, Tao He¹, Haisheng Qian⁶, Shu-Hong Yu⁷

Affiliations

¹ School of Biological and Medical Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China.
² Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, CAS Centre for Excellence in Nanoscience, Hefei Science Centre of CAS, University of Science and Technology of China, Hefei, 230026, PR China.
³ Department of Radiology, Anhui Province Hospital, Hefei, Anhui, 230001, PR China.
⁴ School of Biological and Medical Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China. Electronic address: [email protected].
⁵ Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, PR China.
⁶ School of Biological and Medical Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui, 230009, PR China. Electronic address: [email protected].
⁷ Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Chemistry, CAS Centre for Excellence in Nanoscience, Hefei Science Centre of CAS, University of Science and Technology of China, Hefei, 230026, PR China. Electronic address: [email protected].

PMID: 29304404
DOI: 10.1016/j.biomaterials.2017.12.023

Abstract

There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF₄ nanocrystal (sub-10 nm) was synthesized using a facile high temperature organic solution method, and the nanocrystals were modified by a ligand-exchange approach using PEG-PAA di-block copolymer. The PEG-PAA modified NaGdF₄ nanocrystal (denoted as ppNaGdF₄ nanocrystal) exhibited a high r₁ relaxivity which was twice of commercially used gadopentetate dimeglumine (Gd-DTPA) injection. MR angiography on rabbit using ppNaGdF₄ nanocrystal at a low dose showed enhanced vascular details and long circulation time. Lyophilized powder of ppNaGdF₄ nanocrystals have been successfully prepared without aggregation or reduction of MR performance, indicating the stability and an effective way to store this nanoscale contrast agent. No haemolysis was induced by ppNaGdF₄ nanocrystal, and an extremely low leakage of gadolinium ions was confirmed. Furthermore, efficient renal excretion was one of the clearance pathways of ppNaGdF₄ nanocrystal according to both the time dependent distribution data in blood and tissues and MR images. The in vivo toxicity evaluation further validated the great potential as a clinical agent for blood pool imaging.

Keywords: Compatibility; Contrast agent; Gadolinium based nanocrystals; Lyophilized powder injection; Magnetic resonance angiography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Contrast Media* / chemistry
Gadolinium* / administration & dosage
Gadolinium* / chemistry
Humans
Kidney / diagnostic imaging
Kidney / metabolism
Magnetic Resonance Angiography / methods*
Materials Testing
Nanoparticles* / chemistry
Rabbits

Substances

Contrast Media
Gadolinium