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Updated: May 1, 2026

A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
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.
Abstract:
Metastasis remains the leading cause of cancer-related mortality, yet its early detection is hindered by the subtle and unpredictable nature of the metastatic niche. In this study, we developed a self-assembling peptide-based activatable nanoprobe, 1-CyBr(PBA)-NGR NPs, designed for the early detection of the metastatic niche through circulating tumor cells (CTCs)-mediated hitchhiking and hydrogen peroxide (H2O2)-induced fluorescence activation. The peptide probe spontaneously assembled into stable spherical nanoparticles in aqueous media and undergoes H2O2-triggered fluorescence recovery via oxidation of the phenylboronic acid masking group. Upon intravenous injection, 1-CyBr(PBA)-NGR NPs "hitchhike" CTCs through specific binding via the NGR moiety, utilizing the natural trafficking pathways of CTCs to reach the metastatic lesion. Upon reaching the metastatic site, the nanoparticles are selectively activated by the microenvironment, resulting in fluorescence activation and enabling precise optical imaging of the metastatic site. In vivo imaging in a lung metastatic mouse model revealed distinct fluorescence in the lungs following intravenous administration of 1-CyBr(PBA)-NGR NPs, whereas minimal fluorescence was observed in both the healthy control and antioxidant N-acetylcysteine (NAC)-treated metastatic mice, further confirming the probe's selective activation in response to the elevated H2O2 levels in the metastatic lesion. This study presents a "silent-to-bright" NIR imaging strategy for tumor metastasis monitoring, utilizing CTCs as "hitchhiking" carriers and the metastatic microenvironment as fluorescence activators, offering a promising approach for tumor metastasis diagnosis and intervention.
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.

