VYQFF Peptide-Modified Brucine Liposomes: Antitumor Activity in Head and Neck Squamous Cell Carcinoma and Mechanistic Insights

Abstract

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and conventional chemotherapy has limited efficacy and substantial toxicity. We developed a VYQFF peptide-modified brucine liposome (Bru-VYQFF-Lip) and characterized its particle size, zeta potential, polydispersity, encapsulation efficiency, and drug loading. Bru-VYQFF-Lip showed greater uptake in Trop2-high HSC3 cells than in HOK cells and inhibited HNSCC-cell proliferation, migration, and invasion while promoting apoptosis. After intratumoral administration, the VYQFF-modified formulation showed greater local fluorescence retention than the NHS-bearing, non-peptide comparator; this experiment does not establish systemic tumor targeting or direct Trop2-specific recognition. Bru-VYQFF-Lip also suppressed tumor growth in a nude-mouse xenograft model. Terminal serum chemistry and organ histology did not reveal overt hepatorenal or histopathological injury, although the safety assessment was limited by the absence of complete longitudinal and hematological evaluation. Bioinformatic and experimental analyses identified INHBA as a candidate mediator associated with poor prognosis. Mechanistic experiments were consistent with suppression of the INHBA/TGF-β/Smad axis and epithelial-mesenchymal transition. These findings support further evaluation of VYQFF-functionalized brucine liposomes, including physicochemically matched controls, receptor-blocking studies, systemic biodistribution experiments, and comprehensive toxicology.