Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging

ACS Nano
Yi LuoHeather A Clark

Abstract

A suite of imaging tools for detecting specific chemicals in the central nervous system could accelerate the understanding of neural signaling events critical to brain function and disease. Here, we introduce a class of nanoparticle sensors for the highly specific detection of acetylcholine in the living brain using magnetic resonance imaging. The nanosensor is composed of acetylcholine-catalyzing enzymes and pH-sensitive gadolinium contrast agents co-localized onto the surface of polymer nanoparticles, which leads to changes in T1 relaxation rate (1/ T1). The mechanism of the sensor involves the enzymatic hydrolysis of acetylcholine leading to a localized decrease in pH which is detected by the pH-sensitive gadolinium chelate. The concomitant change in 1/ T1 in vitro measured a 20% increase from 0 to 10 μM acetylcholine concentration. The applicability of the nanosensors in vivo was demonstrated in the rat medial prefrontal cortex showing distinct changes in 1/ T1 induced by pharmacological stimuli. The highly specific acetylcholine nanosensor we present here offers a promising strategy for detection of cholinergic neurotransmission and will facilitate our understanding of brain function through chemical imaging.

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Citations

Mar 13, 2019·Annual Review of Analytical Chemistry·Guoxin RongHeather A Clark
Jun 14, 2019·Contrast Media & Molecular Imaging·Juan PellicoJason J Davis
May 10, 2020·Topics in Current Chemistry·Ashish AvasthiMaría Luisa García-Martín
Feb 25, 2021·ACS Sensors·Hyewon SeoHeather A Clark
Mar 17, 2021·Advanced Biology·Tiancong Ma, Tian Xia
Jun 22, 2021·ACS Omega·Min Kyeong Kang, Jin-Won Park
Mar 24, 2020·ACS Sensors·Julia Ann-Therese WalkerSimon R Corrie

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