Reductive microenvironment responsive gadolinium-based polymers as potential safe MRI contrast agents

Accumulation of nano-scale contrast agents in body tissues potentially induces adverse effects associated with free Gd( iii ) ion release from the nano-scale system, such as nephrogenic systemic fibrosis and gadolinium deposition in the brain tissue. A novel formulation strategy was proposed herein...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials science 2019-04, Vol.7 (5), p.1919-1932
Main Authors: Guo, Shiwei, Xiao, Xueyang, Wang, Xiaoming, Luo, Qiang, Zhu, Hongyan, Zhang, Hu, Li, Haonan, Gong, Qiyong, Luo, Kui
Format: Article
Language:English
Subjects:
Biodegradability
Brain
Chain transfer
Chelates
Chemical bonds
Conjugation
Contrast agents
Copolymers
Fibrosis
Gadolinium
Methacrylamide
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Accumulation of nano-scale contrast agents in body tissues potentially induces adverse effects associated with free Gd( iii ) ion release from the nano-scale system, such as nephrogenic systemic fibrosis and gadolinium deposition in the brain tissue. A novel formulation strategy was proposed herein for Gd-based macromolecular MRI contrast agents (Gd-mCAs), which may significantly reduce Gd( iii ) retention but maintain sufficient imaging contrast. Biodegradable poly[ N -(1,3-dihydroxypropyl)methacrylamide] copolymers (pDHPMA) were synthesized from N -(1,3-dihydroxypropyl)methacrylamide (DHPMA) as a monomer and enzyme-responsive short peptide (GFLG) as a chain transfer agent. Small molecular Gd-chelate (Gd-DOTA) was conjugated onto the copolymer backbone through a sulfide bond or a GSH-sensitive cleavable disulfide bond to produce two novel Gd-mCAs (pDHPMA-Cy5.5-DOTA-Gd or pDHPMA-Cy5.5-SS-DOTA-Gd) for tumor diagnosis. Their relaxivities were 10.49 and 10.24 mM −1 s −1 respectively, which were significantly higher than that of DTPA-Gd (3.97 mM −1 s −1 ). Compared with pDHPMA-Cy5.5-DOTA-Gd, pDHPMA-Cy5.5-SS-DOTA-Gd had a shorter Gd( iii ) retention time but maintained a sufficient contrast efficacy. We have demonstrated that the conjugation of small molecular Gd-chelate to biodegradable macromolecular carriers through a ROX-sensitive biocleavable disulfide bond may be an efficient strategy for formulating safe biodegradable Gd-based pDHPMA copolymers as MRI contrast agents. A ROX and enzyme-responsive biodegradable gadolinium-based mCA was prepared, demonstrating a short gadolinium retention time and sufficient MRI contrast efficacy in tumors.
ISSN:2047-4830
2047-4849
DOI:10.1039/c8bm01103f