Silent-To-Bright CTCs-Hitchhiking Peptide Nanoprobe for Activatable NIR Imaging of Lung Metastasis in Mice

Tingting Zhang1, Xiaoping Chen1, Shiqi Hao1

  • 1Department of Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 210009, China.

Analytical Chemistry
|April 30, 2026
PubMed

Insights

This study introduces a novel peptide-based nanoprobe for early cancer metastasis detection. The probe uses circulating tumor cells (CTCs) for transport and activates fluorescence in response to hydrogen peroxide (H2O2) at the metastatic site.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Metastasis is a primary cause of cancer mortality, challenging early detection due to subtle metastatic niches.
  • Current methods for detecting metastatic sites are limited by the unpredictable nature of tumor spread.

Purpose of the Study:

  • To develop a self-assembling peptide-based nanoprobe for early detection of the metastatic niche.
  • To utilize circulating tumor cells (CTCs) for targeted delivery and hydrogen peroxide (H2O2)-induced fluorescence activation for imaging.

Main Methods:

  • Development of a peptide-based nanoprobe (1-CyBr(PBA)-NGR NPs) that self-assembles and activates fluorescence.
  • Utilizing the NGR moiety for CTCs-mediated hitchhiking for targeted delivery to metastatic lesions.
  • In vivo optical imaging in a lung metastatic mouse model to assess probe performance.

Main Results:

  • The nanoprobe demonstrated H2O2-triggered fluorescence recovery, enabling "silent-to-bright" imaging.
  • In vivo imaging showed distinct lung fluorescence in metastatic mice, with minimal signal in controls or NAC-treated mice.
  • Selective activation by the metastatic microenvironment's elevated H2O2 levels was confirmed.

Conclusions:

  • The developed nanoprobe offers a promising strategy for tumor metastasis monitoring and diagnosis.
  • CTCs serve as effective "hitchhiking" carriers, and the metastatic microenvironment acts as a fluorescence activator.
  • This approach facilitates precise optical imaging for potential tumor metastasis intervention.

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