Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles

Area of Science:

• Nanotechnology
• Oncology
• Medical Imaging

Background:

• Current lymph node metastasis diagnosis relies on dissection and histology, which has limitations.
• Ultra-pH sensitive (UPS) nanoparticles are effective for delineating primary tumor margins in cancer surgery.
• The study explores UPS nanoparticles for detecting cancer in lymph nodes.

Purpose of the Study:

• To investigate the effectiveness of indocyanine green (ICG) conjugated UPS nanoparticles for detecting cancer-involved lymph nodes.
• To compare the diagnostic performance of UPS nanoparticles with different pKₐ values.

Main Methods:

• Synthesized ICG-conjugated UPS nanoparticles with varying pKₐ values (UPS₅.₃, UPS₆.₁, UPS₆.₉).
• Administered nanoparticles systemically in a mouse model and used near-infrared fluorescence imaging to guide lymph node removal.
• Performed ex vivo imaging and histological analysis for quantification and diagnosis.

Main Results:

• UPS nanoparticles exhibited cancer-specific fluorescence clustering within lymph nodes.
• UPS₅.₃ demonstrated high accuracy in detecting metastatic lymph nodes (ROC AUC of 0.96 ± 0.03).
• UPS₆.₁ and UPS₆.₉ showed lower discriminatory power.

Conclusions:

• All tested UPS nanoparticle compositions effectively discriminated between metastatic and benign lymph nodes.
• UPS₅.₃ provided the best performance for detecting lymph node metastasis.
• Detecting very small micro-metastases (< 2 mm) remains a challenge.