A smart magnetic resonance imaging contrast agent responsive to adenosine based on a DNA aptamer-conjugated gadolinium complex

Abstract

We report a general strategy for developing a smart MRI contrast agent for the sensing of small molecules such as adenosine based on a DNA aptamer that is conjugated to a Gd compound and a protein streptavidin. The binding of adenosine to its aptamer results in the dissociation of the Gd compound from the large protein, leading to decreases in the rotational correlation time and thus change of MRI contrast.

Aptamer-based biosensors for biomedical diagnostics

“…The detection was also demonstrated in 10% human serum. 123 Compared to SPION-based MRI contrast agents, gadolinium-based agents are smaller in size and easier for intracellular imaging. A limitation of current MRI contrast agents is that high concentrations are required, and aptamer attachment might help solve this issue by increase specificity.…”

Naphthyridine-based lanthanide complexes worked as magnetic resonance imaging contrast for guanosine 5′-monophosphate in vivo

“…Most prevalently, contrast agent sensors display a change in q in response to a particular analyte [29,30]. The second always attributes to the contrast agent weight change because of the associative or dissociative process between the contrast agents and analytes [31,46]. Finally, tuning water exchange rate (1/τ m ) of nine-coordinate responsive Gd-based constrast agents to invoke a significant relaxivity change involves several factors: steric crowding, coordination geometry and counter ion [47].…”

“…Inspired by the elegant smart contrast agents for the β-galactosidase activity described by Meade et al. [29,30], and adenosine based on aptamer-conjugated gadolinium complex [31], herein, we reported a new naphthyridine-based Gd(III) complex as magnetic resonance imaging contrast towards GMP through the incorporation of a 2-amino-7-methyl-1,8-naphthyridine to a Gd(III) platform. We envisioned that the incorporation of naphthyridine moiety would interact with guanine moiety through Watson-Crick base-pairing [32][33][34]; these interactions relieve steric congestion around the Gd 3 þ center, allowing the phosphate with suitable positions to be coordinated, from which the improvement of the selectivity toward GMP over other ribonucleotide polyphosphates is expected.…”

“…Furthermore, naphthyridine could also act as a sensitizer to lanthanide ion (Eu, Tb), pairing with guanine base, resulting in the luminescence change for the inhibited sensitizing process. Such could be the alternative sensing channel beside the MRI, superior to the most other Gd-based small molecular contrast agents [29][30][31].…”

Imparting the unique properties of DNA into complex material architectures and functions

“…(b) A triparite, fluorescence-quenching assembly [69]. (c) An adenosine-responsive gadolinium MRI contrast agent [70]. (d) Gold nanoparticles (GNP) with adsorbed thrombin binding aptamer (TBA) and SERS active dye will decrease their Raman signal in the presence of thrombin [71].…”