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J Am Chem Soc. 2018 Aug 15;140(32):10071-10074. doi: 10.1021/jacs.8b04169. Epub 2018 Aug 2.

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

Author information

1
Department of Radiology, Sir Run Run Shaw Hospital , Zhejiang University , Hangzhou 310016 , China.
2
Center for Nanoparticle Research , Institute for Basic Science (IBS) , Seoul 08826 , Republic of Korea.
3
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.
4
School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200240 , China.
5
School of Chemical and Biological Engineering , Seoul National University , Seoul 08826 , Republic of Korea.

Abstract

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.

PMID:
30059219
DOI:
10.1021/jacs.8b04169

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