Magnetic Resonance Imaging (MRI) is a powerful imaging modality to non-invasively visualize anatomical detail of the human body with high spatial and temporal resolution. It can further provide chemical information by using bioresponsive contrast agents (CAs). Numerous bioresponsive CAs have been reported for detecting biomarkers such as enzymatic activities, neurotransmitters, metal ions, and extracellular pH (pHe). One approach to enhance the qualitative and quantitative bioresponsive MR signal and address the lack of signal sensitivity in vivo is the use of nanotechnology. DNA nanomaterial has drawn great attention due to its programmability, biocompatibility, reproducibility, and flexible functionalization. DNA possesses high binding specificity, thermodynamic stability, and numerous sequences that can bind to their complementary strands to form a wide range of structures. Applications of DNA-based structures have been explored: such as, tetrahedron, bipyramid, and icosahedron DNA-based nanostructures for in vivo fluorescence, PET, & SPECT imaging. DNA nanomaterials exhibit key biosensor characteristics that would serve effectively as a nanoplatform for quantitative MRI analysis. We recently reported a dendrimer-shaped pH-responsive DNA-based MR-CAs (pH-DMRCA) and validated its pH quantification method. By adapting and optimizing our previous work, we present an acetylcholine-responsive MR-CAs (ACh-DMRCA). Acetylcholine is an important molecular messenger involved in regulating chemical communication between brain cells. Measuring chemical dynamics can lead to greater insights at the synaptic level and help gain a better understanding of molecular neural signaling in the brain. Strategies that modulate the MR signals (longitudinal relaxation time, T1 or transverse relaxation time, T2) from Gd-based pH-sensitive CAs are incorporated into our DNA-based MR-CA (DMRCA) design. In addition, acetylcholine catalyzing enzymes were conjugated onto ACh-DMRCAs as they cause a local decrease in pH which is detected by the pH-sensitive CAs, leading to measurable change in T1 & T2 . ACh-DMRCAs were prepared and shown to be sensitive at various ranges of acetylcholine concentrations. Not only will this new tool serve as a modular platform for sensing other key biological analytes of interest but also will be the first MR CA that can selectively measure neurotransmitter release from the cellular to the anatomical level in a single imaging modality.

DNA based nanostructures as platforms for contrast agents for quantitative MRI analysis

ACS Spring 2022

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