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Research Article

Dual-ratiometric magnetic resonance tunable nanoprobe with acidic-microenvironment-responsive property to enhance the visualization of early tumor pathological changes

Rong Cao1,§Ning Tang2,§Yi Zhu1,§An Chen1Yumeng Li1,3Renbin Ge1Yuan Li2Zhongyi Huang4Jiajing Guo1Jiali Deng1,3Hongwei Lu5( )Ziwei Lu6( )Helen Forgham7Thomas P. Davis7Ruirui Qiao7( )Zhongling Wang1( )
Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
School of food science, Nanjing Xiaozhuang University, Nanjing 211171, China
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
Department of Neurology, School of Medicine, New York University, New York 10016, USA
Department of Biomedical Engineering, College of Engineering, Shantou University, Shantou 515063, China
Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia

§ Rong Cao, Ning Tang, and Yi Zhu contributed equally to this work.

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Graphical Abstract

We developed a dually activatable nanoprobe that leverages hallmarks of disease microenvironment to non-invasively detect pathological changes and ultrasmall lesions at early stage.

Abstract

The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging (MRI), with the advantage of significantly improved specificity and good biocompatibility. However, the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression. Here, we report on a dual-ratiometric magnetic resonance tunable (DMRT) nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles, complexed to a pH responsive biocompatible polymer. This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization, providing exceptional quantitative pathophysiological information in vitro and in vivo. When used in combination with dual-contrast enhancement triple subtraction imaging technique (DETSI), this smart nanoprobe guarantees the diagnosis of early-stage diseases. We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging, as well as microenvironment visualization and disease progression monitoring.

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Nano Research
Pages 10034-10046
Cite this article:
Cao R, Tang N, Zhu Y, et al. Dual-ratiometric magnetic resonance tunable nanoprobe with acidic-microenvironment-responsive property to enhance the visualization of early tumor pathological changes. Nano Research, 2023, 16(7): 10034-10046. https://doi.org/10.1007/s12274-023-5679-x
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Received: 25 December 2022
Revised: 18 March 2023
Accepted: 20 March 2023
Published: 15 April 2023
© Tsinghua University Press 2023
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