Safe and potent MRI contrast agents by complexing gadolinium with enzyme/reduction dual-sensitive branched polymers. (December 2019)

• Record Type: Journal Article
• Authors: Xiaoming, Wang; Shiwei, Guo; Zhiqian, Li; Xueyang, Xiao; Lei, Gu; Qiang, Luo; Hu, Zhang; Qiyong, Gong; Kui, Luo
• Is Part Of: Applied materials today. Volume 17(2019)
• Page Start: 92
• Page End: 103
• Publication Date: 2019-12
• Subjects: Gd-based contrast agents -- Branched DHPMA copolymers -- Enzyme/reduction dual-sensitivity -- Biosafety -- Efficiency; Materials science -- Periodicals; Materials -- Research -- Periodicals; 620.1105
• DOI: 10.1016/j.apmt.2019.07.019
• Languages: English
• ISSNs: 2352-9407

Abstract

Abstract: To address the issue of inefficient signal enhancement by polymeric magnetic resonance imaging (MRI) contrast agents, herein, we have prepared a high molecular-weight (MW) branched and gadolinium (Gd)-labeled N -(1, 3-dihydroxypropyl)methacrylamide (DHPMA) copolymer (branched-pDHPMA-SS-Gd, 192 kDa, about 110 nm) by linking each branched chain by an enzyme-sensitive tetrapeptide (GFLG), and small molecule DOTA-Gd was conjugated to the carrier with a reduction-sensitive disulfide bond to obtain an enzyme/reduction dual-sensitive contrast agent. For control studies, DOTA-Gd was conjugated to an enzyme-sensitive branched carrier without a disulfide bond, resulting in a single sensitive branched copolymer (branched-pDHPMA-Gd, 198 kDa, about 110 nm). The longitudinal relaxivities of branched-pDHPMA-SS-Gd (r1 = 12.48 mM −1 s −1 ) and branched-pDHPMA-Gd (r1 = 14.37 mM −1 s −1 ) were 3–4 folds of clinical DTPA-Gd (r1 = 3.53 mM −1 s −1 ). The in vivo imaging signal enhancement by branched-pDHPMA-SS-Gd (about 130%) was similar to that of branched-pDHPMA-Gd (120%), which was 2.4 to 2.6-fold higher than that of clinical DTPA-Gd (about 50%). Although branched copolymers had the similar capability in enhancing MRI signals, enzyme/reduction dual-sensitive branched-pDHPMA-SS-Gd released low MW Gd-chelates at a more rapid rate, rendering it better biosafety and biodegradability. In conclusion, this study provides an important theoretical and experimental foundation for construction of Gd-based multi-sensitive polymeric MRI contrast agents with great biosafety and high efficiency.