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Highly Sensitive Diagnosis of Small Hepatocellular Carcinoma Using pH-Responsive Iron Oxide Nanocluster Assemblies

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    Highly Sensitive Diagnosis of Small Hepatocellular Carcinoma Using pH-Responsive Iron Oxide Nanocluster Assemblies
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    • Jingxiong Lu
      Jingxiong Lu
      Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Jingxiong Lu
      Orcidhttp://orcid.org/0000-0002-2032-3216
    • Jihong Sun
      Jihong Sun
      Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
      More by Jihong Sun
    • Fangyuan Li
      Fangyuan Li
      Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences  and  MOE Key Laboratory of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China
      More by Fangyuan Li
    • Jin Wang
      Jin Wang
      Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
      More by Jin Wang
    • Jianan Liu
      Jianan Liu
      Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
      More by Jianan Liu
    • Dokyoon Kim
      Dokyoon Kim
      Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
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    • Chunhai Fan
      Chunhai Fan
      Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
      School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
      More by Chunhai Fan
      Orcidhttp://orcid.org/0000-0002-7171-7338
    • Taeghwan Hyeon
      Taeghwan Hyeon
      Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
      School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
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    • Daishun Ling*
      Daishun Ling
      Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences  and  MOE Key Laboratory of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China
      *[email protected]
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      Orcidhttp://orcid.org/0000-0002-9977-0237
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2018, 140, 32, 10071–10074
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    https://doi.org/10.1021/jacs.8b04169
    Published July 30, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Iron oxide nanoparticle (IONP)-based magnetic resonance imaging (MRI) contrast agents have been widely used for the diagnosis of hepatic lesions. However, current IONP-based liver-specific MRI contrast agents rely on single-phase contrast enhancement of the normal liver, which is not sensitive enough to detect early stage small hepatocellular carcinomas (HCCs). We herein report i-motif DNA-assisted pH-responsive iron oxide nanocluster assemblies (termed RIAs), which provide an inverse contrast enhancemt effect to improve the distinction between normal liver and target HCC tissues. The acidic pH of the tumor microenvironment triggers the disassembly of the RIAs, which leads to a drastic decrease in their relaxivity ratio (r2/r1), thus converting the RIAs from a T2 to T1 contrast agent. This inverse contrast enhancement of normal liver darkening and HCC brightening under T1 imaging mode was validated on an orthotopic HCC model. Our design provides a novel strategy for the exploitation of the next-generation intelligent MRI contrast agents.

    Copyright © 2018 American Chemical Society

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