ACS Publications. Most Trusted. Most Cited. Most Read
Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Nano 2018, 12, 6, 5761-5773
    Article

    Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging
    Click to copy article linkArticle link copied!

    Other Access OptionsSupporting Information (1)

    ACS Nano

    Cite this: ACS Nano 2018, 12, 6, 5761–5773
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.8b01640
    Published May 31, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    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/T1in 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.

    Copyright © 2018 American Chemical Society

    Subjects

    what are subjects

    Keywords

    what are keywords

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.8b01640.

    • Fabrication of pH-MRNS and ACh-MRNS, structure and 1H NMR spectrum of the pH-sensitive chelator, TEM image of the ACh-MRNS using NanoVan stain, in vitro nanosensor to pH dependence, pH change in the mixture of the nanosensor and acetylcholine, xylenol orange test, kinetics of BuChE, relative signal intensity at different TR, histology, and diffusion of pH-MRNS in phantom brain (Figures S1–S11) (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 36 publications.

    1. Giovanni Giammanco, Remi Veneziano, Bryce Dunn, Nicholas Such, John R. Cressman, Parag V. Chitnis. DNA-Based Near-Infrared Voltage Sensors. ACS Sensors 2023, 8 (10) , 3680-3686. https://doi.org/10.1021/acssensors.3c01429
    2. Dorian Foster, Jessica Larsen. Polymeric Metal Contrast Agents for T1-Weighted Magnetic Resonance Imaging of the Brain. ACS Biomaterials Science & Engineering 2023, 9 (3) , 1224-1242. https://doi.org/10.1021/acsbiomaterials.2c01386
    3. Min Kyeong Kang, Jin-Won Park. Acetylcholine Detection Based on pH-Sensitive Liposomes. ACS Omega 2021, 6 (23) , 14963-14967. https://doi.org/10.1021/acsomega.1c01023
    4. Hyewon Seo, Kristine Y. Ma, Erin E. Tuttle, Isen Andrew C. Calderon, Alissa D. Buskermolen, Chris A. Flask, Heather A. Clark. A DNA-Based MRI Contrast Agent for Quantitative pH Measurement. ACS Sensors 2021, 6 (3) , 727-732. https://doi.org/10.1021/acssensors.1c00296
    5. Chandran Murugan, Nagaraj Murugan, Ashok K. Sundramoorthy, Anandhakumar Sundaramurthy. Gradient Triple-Layered ZnS/ZnO/Ta2O5–SiO2 Core–Shell Nanoparticles for Enzyme-Based Electrochemical Detection of Cancer Biomarkers. ACS Applied Nano Materials 2020, 3 (8) , 8461-8471. https://doi.org/10.1021/acsanm.0c01949
    6. Julia Ann-Therese Walker, Xiaowei Wang, Karlheinz Peter, Kristian Kempe, Simon R. Corrie. Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo. ACS Sensors 2020, 5 (4) , 1190-1197. https://doi.org/10.1021/acssensors.0c00245
    7. Yongzhen Dong, Wenshu Zheng, Da Chen, Xiujuan Li, Jia Wang, Zhilong Wang, Yiping Chen. Click Reaction-Mediated T2 Immunosensor for Ultrasensitive Detection of Pesticide Residues via Brush-like Nanostructure-Triggered Coordination Chemistry. Journal of Agricultural and Food Chemistry 2019, 67 (35) , 9942-9949. https://doi.org/10.1021/acs.jafc.9b03463
    8. Guoxin Rong, Eric H. Kim, Yi Qiang, Wenjun Di, Yiding Zhong, Xuanyi Zhao, Hui Fang, Heather A. Clark. Imaging Sodium Flux during Action Potentials in Neurons with Fluorescent Nanosensors and Transparent Microelectrodes. ACS Sensors 2018, 3 (12) , 2499-2505. https://doi.org/10.1021/acssensors.8b00903
    9. Mireia Perera-Gonzalez, Christina J. MacAskill, Heather A. Clark, Chris A. Flask. Fast quantitative MRI: Spiral Acquisition Matching-Based Algorithm (SAMBA) for Robust T1 and T2 Mapping. Journal of Magnetic Resonance Open 2024, 20 , 100157. https://doi.org/10.1016/j.jmro.2024.100157
    10. Yang Liu, Lingling Guo, Ping Jin, Liqiang Liu, Xinxin Xu, Chuanlai Xu, Liguang Xu, Hua Kuang. Greenness metrics of immunoassays for the detection of organophosphorus pesticide residues. TrAC Trends in Analytical Chemistry 2024, 178 , 117828. https://doi.org/10.1016/j.trac.2024.117828
    11. Kristine Y. Ma, Mireia Perera-Gonzalez, Nicole I. Langlois, Owen M. Alzubi, Joseph D. Guimond, Chris A. Flask, Heather A. Clark. pH-responsive i-motif-conjugated nanoparticles for MRI analysis. Sensors & Diagnostics 2024, 3 (4) , 623-630. https://doi.org/10.1039/D3SD00285C
    12. Zhuangzhuang Guo, Xin Wang, Hao-Ling Sun. Constructing a novel pH-mediated magnetic relaxation sensor via the Mn(II)/Mn(IV) conversion. Microchemical Journal 2024, 196 , 109677. https://doi.org/10.1016/j.microc.2023.109677
    13. Rajapriya Govindaraju, Saravanan Govindaraju, Kyusik Yun, Jongsung Kim. Fluorescent-Based Neurotransmitter Sensors: Present and Future Perspectives. Biosensors 2023, 13 (12) , 1008. https://doi.org/10.3390/bios13121008
    14. Paweł Świt, Aleksandra Pollap, Joanna Orzeł. Spectroscopic Determination of Acetylcholine (ACh): A Representative Review. Topics in Current Chemistry 2023, 381 (4) https://doi.org/10.1007/s41061-023-00426-9
    15. Farbod Amirghasemi, Ali Soleimani, Shahd Bawarith, Asna Tabassum, Alayne Morrel, Maral P. S. Mousavi. FAST (Flexible Acetylcholine Sensing Thread): Real-Time Detection of Acetylcholine with a Flexible Solid-Contact Potentiometric Sensor. Bioengineering 2023, 10 (6) , 655. https://doi.org/10.3390/bioengineering10060655
    16. Zhichao Liu, Ying Zhu, Liming Zhang, Weiping Jiang, Yawei Liu, Qiaowei Tang, Xiaoqing Cai, Jiang Li, Lihua Wang, Changlu Tao, Xianzhen Yin, Xiaowei Li, Shangguo Hou, Dawei Jiang, Kai Liu, Xin Zhou, Hongjie Zhang, Maili Liu, Chunhai Fan, Yang Tian. Structural and functional imaging of brains. Science China Chemistry 2023, 66 (2) , 324-366. https://doi.org/10.1007/s11426-022-1408-5
    17. Sadia Batool, Hafezeh Nabipour, Seeram Ramakrishna, Masoud Mozafari. Nanotechnology and quantum science enabled advances in neurological medical applications: diagnostics and treatments. Medical & Biological Engineering & Computing 2022, 60 (12) , 3341-3356. https://doi.org/10.1007/s11517-022-02664-3
    18. Yawen Wang, Minye Zhan, Alard Roebroeck, Peter De Weerd, Sriranga Kashyap, Mark J. Roberts. Inconsistencies in atlas-based volumetric measures of the human nucleus basalis of Meynert: A need for high-resolution alternatives. NeuroImage 2022, 259 , 119421. https://doi.org/10.1016/j.neuroimage.2022.119421
    19. Jason Yun, Michelle Baldini, Rochishnu Chowdhury, Arnab Mukherjee. Designing Protein‐Based Probes for Sensing Biological Analytes with Magnetic Resonance Imaging. Analysis & Sensing 2022, 2 (5) https://doi.org/10.1002/anse.202200019
    20. Mireia Perera-Gonzalez, Kristine Y. Ma, Chris A. Flask, Heather A. Clark. In vitro Testbed Platform for Evaluating Small Volume Contrast Agents via Magnetic Resonance Imaging. 2022, 572-576. https://doi.org/10.1109/DSD57027.2022.00082
    21. Leyla Amirifar, Amir Shamloo, Rohollah Nasiri, Natan Roberto de Barros, Ze Zhong Wang, Bige Deniz Unluturk, Alberto Libanori, Oleksandr Ievglevskyi, Sibel Emir Diltemiz, Samuel Sances, Ilangko Balasingham, Stephanie K. Seidlits, Nureddin Ashammakhi. Brain-on-a-chip: Recent advances in design and techniques for microfluidic models of the brain in health and disease. Biomaterials 2022, 285 , 121531. https://doi.org/10.1016/j.biomaterials.2022.121531
    22. Ayland C. Letsinger, Zhenglin Gu, Jerrel L. Yakel. α7 nicotinic acetylcholine receptors in the hippocampal circuit: taming complexity. Trends in Neurosciences 2022, 45 (2) , 145-157. https://doi.org/10.1016/j.tins.2021.11.006
    23. He Wei, Abigail M Frey, Alan Jasanoff. Molecular fMRI of neurochemical signaling. Journal of Neuroscience Methods 2021, 364 , 109372. https://doi.org/10.1016/j.jneumeth.2021.109372
    24. Xuan Gu, Xiaoying Wang. An overview of recent analysis and detection of acetylcholine. Analytical Biochemistry 2021, 632 , 114381. https://doi.org/10.1016/j.ab.2021.114381
    25. Xiao Liang, Yong Liu, Kai Wen, Wei Jiang, Quanshun Li. Immobilized enzymes in inorganic hybrid nanoflowers for biocatalytic and biosensing applications. Journal of Materials Chemistry B 2021, 9 (37) , 7597-7607. https://doi.org/10.1039/D1TB01476E
    26. Shengxiang Fu, Zhongyuan Cai, Hua Ai. Stimulus‐Responsive Nanoparticle Magnetic Resonance Imaging Contrast Agents: Design Considerations and Applications. Advanced Healthcare Materials 2021, 10 (5) https://doi.org/10.1002/adhm.202001091
    27. Yunyun Hu, Xin Guo, Peilin Gu, Qin Luo, Yang Song, Erqun Song. Mn2+-mediated magnetic relaxation switching for direct assay of ctDNA in whole blood via exonuclease III assisted amplification. Sensors and Actuators B: Chemical 2021, 330 , 129340. https://doi.org/10.1016/j.snb.2020.129340
    28. Tiancong Ma, Tian Xia. Nanoparticle‐Based Activatable Probes for Bioimaging. Advanced Biology 2021, 5 (1) https://doi.org/10.1002/adbi.202000193
    29. Yi Su, Sumin Bian, Mohamad Sawan. Real-time in vivo detection techniques for neurotransmitters: a review. The Analyst 2020, 145 (19) , 6193-6210. https://doi.org/10.1039/D0AN01175D
    30. A. M. Sergeev, A. P. Pozdnyakov, D. O. Ivanov, E. E. Atamanova, O. V. Olshansky, O. F. Pozdnyakova, L. R. Suf El-Zhil, S. V. Grechaniy. THE RESULTS OF A STUDY OF THE BRAIN IN CHILDREN WITH AUTISM SPECTRUM DISORDERS USING PROTON MAGNETIC RESONANCE SPECTROSCOPY. Diagnostic radiology and radiotherapy 2020, 11 (2) , 66-75. https://doi.org/10.22328/2079-5343-2020-11-2-66-75
    31. Ashish Avasthi, Carlos Caro, Esther Pozo-Torres, Manuel Pernia Leal, María Luisa García-Martín. Magnetic Nanoparticles as MRI Contrast Agents. Topics in Current Chemistry 2020, 378 (3) https://doi.org/10.1007/s41061-020-00302-w
    32. Nidhi Chauhan, Shringika Soni, Prabhudatt Agrawal, Yatan Pal Singh Balhara, Utkarsh Jain. Recent advancement in nanosensors for neurotransmitters detection: Present and future perspective. Process Biochemistry 2020, 91 , 241-259. https://doi.org/10.1016/j.procbio.2019.12.016
    33. Connor M. Ellis, Juan Pellico, Jason J. Davis. Magnetic Nanoparticles Supporting Bio-responsive T1/T2 Magnetic Resonance Imaging. Materials 2019, 12 (24) , 4096. https://doi.org/10.3390/ma12244096
    34. Qiwen Peng, Xueyan Yan, Xinran Shi, Shanshan Ou, Hui Gu, Xiaoxing Yin, Guoyue Shi, Yanyan Yu. In vivo monitoring of superoxide anion from Alzheimer's rat brains with functionalized ionic liquid polymer decorated microsensor. Biosensors and Bioelectronics 2019, 144 , 111665. https://doi.org/10.1016/j.bios.2019.111665
    35. Guoxin Rong, Erin E. Tuttle, Ashlyn Neal Reilly, Heather A. Clark. Recent Developments in Nanosensors for Imaging Applications in Biological Systems. Annual Review of Analytical Chemistry 2019, 12 (1) , 109-128. https://doi.org/10.1146/annurev-anchem-061417-125747
    36. Juan Pellico, Connor M. Ellis, Jason J. Davis. Nanoparticle-Based Paramagnetic Contrast Agents for Magnetic Resonance Imaging. Contrast Media & Molecular Imaging 2019, 2019 , 1-13. https://doi.org/10.1155/2019/1845637
    Download PDF
    Go to ACS Nano
    Get e-Alerts
    Get e-Alerts

    ACS Nano

    Cite this: ACS Nano 2018, 12, 6, 5761–5773
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.8b01640
    Published May 31, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

    Article Views

    2279

    Altmetric

    -

    Citations

    36
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.