Near-infrared emitting polymer nanogels for efficient sentinel lymph node mapping.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Surgical Oncology

Background:

• Sentinel lymph node (SLN) mapping is crucial for predicting cancer metastasis.
• Current methods face limitations in sensitivity and real-time visualization.
• Development of advanced imaging probes is essential for improving surgical accuracy.

Purpose of the Study:

• To develop and characterize a novel near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) for enhanced SLN mapping.
• To evaluate the photostability, lymph node uptake, and retention of NIR-PNG compared to free dye.
• To assess the utility of NIR-PNG for real-time lymphatic imaging in preclinical models.

Main Methods:

• Synthesis of biodegradable pullulan-cholesterol polymer nanogels conjugated with IRDye800 (NIR-PNG).
• Evaluation of nanogel hydrodynamic diameter, photostability, and fluorescence properties.
• Intradermal injection in mice and pigs to assess lymphatic migration, SLN uptake, and retention using NIR imaging.
• Immunohistofluorescence studies to identify cell co-localization within the SLN.

Main Results:

• Developed NIR-PNG with optimal hydrodynamic diameter (~30 nm) for lymph node uptake.
• NIR-PNG exhibited superior photostability and longer retention time in lymph nodes compared to free IRDye800.
• Rapid migration of NIR-PNG to axillary lymph nodes within 2 minutes in mice.
• Real-time imaging of lymphatic flow and precise SLN identification within 1 minute in pigs.
• NIR-PNG nanoprobes were found to co-localize with macrophages and dendritic cells in SLN.

Conclusions:

• The developed NIR-PNG nanoprobes offer enhanced photostability and retention for SLN mapping.
• NIR-PNG facilitates efficient lymphatic visualization and SLN identification in preclinical models.
• These polymer nanoprobes show significant potential for improving cancer surgery, particularly in SLN mapping procedures.