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Chitosan/PCL nanoparticles can improve anti-neoplastic activity of 5-fluorouracil in head and neck cancer through autophagy activation.
de Lima, Jefferson Muniz; Castellano, Lucio Roberto Cançado; Bonan, Paulo Rogério Ferreti; de Medeiros, Eliton Souto; Hier, Michael; Bijian, Krikor; Alaoui-Jamali, Moulay A; da Cruz Perez, Danyel Elias; da Silva, Sabrina Daniela.
Affiliation
  • de Lima JM; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmac
  • Castellano LRC; Health Technician School, Federal University of Paraiba (UFPB), Joao Pessoa, PB, Brazil.
  • Bonan PRF; Department of Oral Pathology, Faculty of Dentistry, Federal University of Paraiba (UFPB), Joao Pessoa, PB, Brazil.
  • de Medeiros ES; Department of Materials Engineering, Federal University of Paraiba (UFPB), Joao Pessoa, PB, Brazil.
  • Hier M; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada.
  • Bijian K; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada.
  • Alaoui-Jamali MA; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada.
  • da Cruz Perez DE; Department of Clinical and Preventive Dentistry, School of Dentistry, Federal University of Pernambuco, Recife, PE, Brazil.
  • da Silva SD; Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada; Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmac
Int J Biochem Cell Biol ; 134: 105964, 2021 05.
Article in En | MEDLINE | ID: mdl-33667680
ABSTRACT
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) microparticles (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. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyesters / Chitosan / Nanoparticles / Head and Neck Neoplasms / Antimetabolites, Antineoplastic Limits: Animals / Humans Language: En Journal: Int J Biochem Cell Biol Journal subject: BIOQUIMICA Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyesters / Chitosan / Nanoparticles / Head and Neck Neoplasms / Antimetabolites, Antineoplastic Limits: Animals / Humans Language: En Journal: Int J Biochem Cell Biol Journal subject: BIOQUIMICA Year: 2021 Document type: Article