A Bioinspired Nanoprobe with Multilevel Responsive T1-Weighted MR Signal-Amplification Illuminates Ultrasmall Metastases

Yao Li, Xiao Zhao, Xiaoli Liu, Keman Cheng, Xuexiang Han, Yinlong Zhang, Huan Min, Guangna Liu, Junchao Xu, Jian Shi, Hao Qin, Haiming Fan, Lei Ren, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Metastasis remains the major cause of death in cancer patients. Thus, there is a need to sensitively detect tumor metastasis, especially ultrasmall metastasis, for early diagnosis and precise treatment of cancer. Herein, an ultrasensitive T1-weighted magnetic resonance imaging (MRI) contrast agent, UMFNP-CREKA is reported. By conjugating the ultrasmall manganese ferrite nanoparticles (UMFNPs) with a tumor-targeting penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala), ultrasmall breast cancer metastases are accurately detected. With a behavior similar to neutrophils' immunosurveillance process for eliminating foreign pathogens, UMFNP-CREKA exhibits a chemotactic “targeting-activation” capacity. UMFNP-CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin-fibronectin complexes, which are abundant around tumors, and then release of manganese ions (Mn2+) to the metastasis in response to pathological parameters (mild acidity and elevated H2O2). The localized release of Mn2+ and its interaction with proteins affects a marked amplification of T1-weighted magnetic resonance (MR) signals. In vivo T1-weighted MRI experiments reveal that UMFNP-CREKA can detect metastases at an unprecedented minimum detection limit of 0.39 mm, which has significantly extended the detection limit of previously reported MRI probe.

Original languageEnglish (US)
Article number1906799
Pages (from-to)e1906799
JournalAdvanced Materials
Issue number4
StatePublished - Jan 1 2020


  • T-weighted detection
  • magnetic resonance imaging (MRI)
  • metastases
  • signal-amplification
  • ultrasmall manganese ferrite nanoparticles
  • Contrast Media/chemistry
  • Hydrogen Peroxide/metabolism
  • Humans
  • Signal-To-Noise Ratio
  • Manganese Compounds/chemistry
  • Magnetic Resonance Imaging/methods
  • Transplantation, Heterologous
  • Oligopeptides/chemistry
  • Fibronectins/chemistry
  • Fibrin/chemistry
  • Breast Neoplasms/diagnosis
  • Neoplasm Metastasis
  • Animals
  • Nanoparticles/chemistry
  • Cell Line, Tumor
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Ferric Compounds/chemistry

ASJC Scopus subject areas

  • Mechanics of Materials
  • Mechanical Engineering
  • Materials Science(all)


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