Precision Visualization of Tumor Microenvironment via a Lysosome-Anchored Molecular Rotor with Viscosity-Triggered...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Cancer Diagnostics

Background:

• Intracellular viscosity is a critical biomarker of the tumor microenvironment.
• Existing probes often lack tumor-targeting capabilities, hindering accurate detection and imaging.
• Novel strategies are needed to enhance tumor visualization and analysis.

Purpose of the Study:

• To develop a novel fluorescent probe (NM-Lys) for sensitive and selective intracellular viscosity sensing.
• To engineer a targeted nanoprobe (Lip-NM-FA) for enhanced tumor imaging.
• To evaluate the probe's efficacy in visualizing tumor boundaries in a preclinical model.

Main Methods:

• Design and synthesis of NM-Lys based on restricted intramolecular motion.
• Evaluation of NM-Lys selectivity and sensitivity for viscosity.
• Development of folic acid-functionalized liposomes (Lip-NM-FA) for targeted delivery.
• In vivo fluorescence imaging of tumors in a xenograft mouse model.

Main Results:

• NM-Lys showed a 21-fold fluorescence enhancement in high-viscosity environments with high selectivity.
• The probe successfully targeted lysosomes and monitored viscosity changes.
• Lip-NM-FA enabled high-contrast visualization of tumor boundaries in mice.
• Targeting the tumor's high-viscosity microenvironment facilitated accurate imaging.

Conclusions:

• NM-Lys is a robust tool for intracellular viscosity sensing.
• Targeted nanoprobes can effectively visualize tumor boundaries.
• This approach offers a promising strategy for tumor monitoring and diagnosis.