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Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
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Color-Convertible, Unimolecular, Micelle-Based, Activatable Fluorescent Probe for Tumor-Specific Detection and

Yu Huang1, Feng Qiu2, Dong Chen1

  • 1School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Small (Weinheim an Der Bergstrasse, Germany)
|April 7, 2017
PubMed
Summary

This study introduces a novel fluorescent nanoprobe for cancer diagnosis that activates in response to hydrogen peroxide (H2O2), a common tumor marker. This ligand-free probe offers universal tumor detection by changing color from blue to green in cancerous cells.

Keywords:
activatable probescancer diagnosiscolor-conversionconjugated polymersunimolecular micelles

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Molecular Imaging

Background:

  • Conventional cancer diagnostic probes often rely on tumor-targeting ligands, leading to variable efficiency across different cancer types.
  • Tumor microenvironments exhibit unique characteristics, such as elevated hydrogen peroxide (H2O2) levels, which can be exploited for diagnosis.
  • Developing universal, ligand-free probes that respond to common tumor features is crucial for improved cancer diagnosis.

Purpose of the Study:

  • To develop a novel, color-convertible, activatable fluorescent nanoprobe for tumor-specific diagnosis.
  • To create a probe that responds to the universal tumor microenvironment hallmark of up-regulated hydrogen peroxide (H2O2).
  • To demonstrate the probe's efficacy in distinguishing tumors from normal tissues without the need for targeting ligands.

Main Methods:

  • Construction of a unimolecular micelle using a hydrophobic poly(fluorene-co-2,1,3-benzothiadiazole) core and hydrophilic poly(ethylene glycol) arms via boronate coupling.
  • Development of an H2O2-activatable fluorescent nanoprobe utilizing an aggregation-enhanced fluorescence resonance energy transfer (AEFRET) strategy.
  • In vitro and in vivo evaluation of the nanoprobe's fluorescence response in normal and cancer cells, and in tumor-bearing mice.

Main Results:

  • The nanoprobe exhibited blue fluorescence in normal cells and switched to strong green emission in various cancer cells.
  • Intravenous injection in tumor-bearing mice resulted in specific green fluorescent signals localized to tumor tissues.
  • In vivo and ex vivo imaging, along with immunofluorescence analysis, confirmed the probe's tumor-specific detection capabilities.

Conclusions:

  • A novel H2O2-activatable, color-convertible fluorescent nanoprobe was successfully developed for tumor-specific diagnosis.
  • The ligand-free probe leverages the universal tumor microenvironment (elevated H2O2) for detection, overcoming limitations of conventional probes.
  • This facile methodology offers a promising platform for developing advanced molecular probes for cancer detection and imaging.