Nanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu

Abstract

Current magnetic resonance imaging (MRI) contrast agents often produce insufficient contrast for diagnosis of early disease stages, and do not sense their biochemical environments. Herein, we report a highly sensitive nanoparticle-based MRI probe with r₁ relaxivity up to 51.7 ± 1.2 mM⁻¹ s⁻¹ (3T). Nanoparticles were co-assembled from Gd³⁺ complexed to heparin–poly(dimethylsiloxane) copolymer, and a reduction-sensitive amphiphilic peptide serving to induce responsiveness to environmental changes. The release of the peptide components leads to a r₁ relaxivity increase under reducing conditions and increases the MRI contrast. In addition, this MRI probe has several advantages, such as a low cellular uptake, no apparent cellular toxicity (tested up to 1 mM Gd³⁺), absence of an anticoagulation property, and a high shelf stability (no increase in free Gd³⁺ over 7 months). Thus, this highly sensitive T₁ MRI contrast nanoparticle system represents a promising probe for early diagnosis through possible accumulation and contrast enhancement within reductive extracellular tumour tissue.