PCL Nanoparticles Enhances Anti-Neoplastic Activity of 5-Fluorouracil in Head CancerAuthor(s): Liliam Takayama*
Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) micro particles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE %) and in vitro drug release profile. The anti- cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively.