Novel Peptide NIRF Optical Surgical Navigation Agents for HNSCC.

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Oncology

Background:

• Head and neck squamous cell carcinoma (HNSCC) has poor survival rates and high recurrence after surgery.
• Current treatments lack effective methods for real-time surgical guidance.
• The peptide HN1 shows promise for targeting HNSCC but has slow cellular accumulation.

Purpose of the Study:

• To develop modified HN1 peptides with improved uptake kinetics for optical surgical navigation (OSN).
• To create IRdye800-labeled peptide adducts for enhanced HNSCC imaging.
• To evaluate the efficacy of novel peptides in vitro and in vivo.

Main Methods:

• Synthesis and chemical characterization of eleven novel HN1-based molecules.
• In vitro assessment of cell uptake kinetics in human HNSCC (Cal 27) cells.
• In vivo imaging of HNSCC xenograft mouse models using IRdye800-labeled peptides.
• Microscopy to confirm cellular localization and binding.

Main Results:

• Modified HN1 peptides with N-terminal lipophilic substitution and resequencing showed markedly increased cell uptake.
• The fastest peptide, 4Iphf-HN17, demonstrated a 26-fold greater uptake rate compared to the original HN1.
• 4Iphf-HN17-IR800 exhibited superior OSN imaging intensity and tumor-to-background contrast in mice.

Conclusions:

• Optimized HN1 peptide structures significantly enhance cellular uptake kinetics.
• The novel 4Iphf-HN17-IR800 conjugate is a promising candidate for OSN in HNSCC.
• Improved imaging agents can enhance surgical precision and patient outcomes for HNSCC.