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Issue 5, 2019
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Reductive microenvironment responsive gadolinium-based polymers as potential safe MRI contrast agents

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Abstract

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.

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

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Publication details

The article was received on 08 Sep 2018, accepted on 31 Jan 2019 and first published on 04 Feb 2019


Article type: Paper
DOI: 10.1039/C8BM01103F
Citation: Biomater. Sci., 2019,7, 1919-1932

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

    S. Guo, X. Xiao, X. Wang, Q. Luo, H. Zhu, H. Zhang, H. Li, Q. Gong and K. Luo, Biomater. Sci., 2019, 7, 1919
    DOI: 10.1039/C8BM01103F

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