pH-responsive i-motif-conjugated nanoparticles for MRI analysis

28 October 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Gadolinium (Gd)-based contrast agents (CA) are widely used to enhance anatomical details in magnetic resonance imaging (MRI). Significant research has expanded the field of CAs into bioresponsive CAs by modulating the signal to image and monitor biochemical processes, such as pH. In this work, we introduce the modular, dynamic actuation mechanism of DNA-based nanostructures as a new way to modulate the MRI signal based on rotational correlation time, τR. We combined a pH-responsive oligonucleotide (i-motif) and a clinical standard CA (Gd-DOTA), to develop a pH-responsive MRI CA. The i-motif folds into a quadruplex in acidic conditions and was incorporated onto gold nanoparticles (iM-GNP) to achieve increased relaxivity, r1, compared to unbound i-motif. In vitro, iM-GNP resulted in a significant increase in r1 over a decreasing pH range (7.5 - 4.5) with a calculated pKa = 5.88 ± 0.01 and a 16.7% change per 0.1 pH unit. In comparison, the control CA with a non-responsive DNA strand (T33-GNP) did not show a significant change in r1 over the same pH range. To demonstrate the potential for performance in tissue, CAs were evaluated in an ex vivo rat brain model. When compared to pre-contrast signal intensity (1/T1), the response to a simulated acidic microenvironment was over 5 times higher than the signal measured in a physiological pH. This approach paves a path for novel programmable, dynamic DNA-based complexes for τR-modulated bioresponsive MRI CAs.


contrast agents
gold nanoparticles

Supplementary materials

Supporting Information
Experimental details, oligonucleotide sequences, gel and HPLC characterization, control T33-GNP relaxivity, single i-motif + Gd-DOTA relaxivity profiles, in-vitro test bed description, and representative raw MRI signal plots.


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