Cancer-Microenvironment-Sensitive Activatable Quantum Dot Probe in the Second Near-Infrared Window

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Quantum Dots

Background:

• Second near-infrared (NIR-II) fluorescence imaging (1000-1700 nm) offers deep tissue penetration and high resolution.
• Development of bright, compact, and controllable NIR-II fluorophores remains a challenge.
• Enzyme-activatable probes are crucial for targeted molecular imaging in complex biological environments.

Purpose of the Study:

• To develop a novel enzyme-activatable probe for NIR-II fluorescence imaging.
• To achieve sophisticated control over NIR-II probe activation based on tumor microenvironment biomarkers.
• To enhance tumor-specific signal detection in vivo.

Main Methods:

• Synthesis of bright and stable PbS/CdS/ZnS core/shell/shell quantum dots (QDs) as NIR-II fluorophores.
• Attachment of activatable modulators exploiting photoexcited electron transfer (PET) quenching via methylene blue.
• Optimization of surface ligands for enzyme accessibility and signal modulation.
• In vivo evaluation using a colon cancer mouse model and optical phantom experiments.

Main Results:

• The synthesized QDs demonstrated bright and stable NIR-II fluorescence.
• The enzyme-activatable probe showed selective fluorescence activation upon matrix metalloprotease activity.
• A 3-fold signal enhancement was observed at tumor sites within 10 minutes in a colon cancer model.
• The NIR-II probe exhibited superior performance compared to conventional first near-infrared dyes.

Conclusions:

• The developed enzyme-activatable NIR-II probe enables precise tumor visualization through deep tissue imaging.
• The probe's design allows for effective modulation of fluorescence based on specific enzyme activity in the tumor microenvironment.
• This technology holds promise for advancing targeted cancer diagnostics and theranostics.