Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer

• Published in: Molecular pharmaceutics Vol. 16; no. 6; pp. 2326 - 2341
• Main Authors: Karavasili, Christina, Andreadis, Dimitrios A, Katsamenis, Orestis L, Panteris, Emmanuel, Anastasiadou, Pinelopi, Kakazanis, Zacharias, Zoumpourlis, Vasilis, Markopoulou, Catherine K, Koutsopoulos, Sotirios, Vizirianakis, Ioannis S, Fatouros, Dimitrios G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.06.2019
• Subjects: Animals; Apoptosis - drug effects; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Curcumin - chemistry; Curcumin - therapeutic use; Doxorubicin - chemistry; Doxorubicin - therapeutic use; Drug Delivery Systems - methods; Female; Flow Cytometry; Head and Neck Neoplasms - drug therapy; Humans; Hydrogels - chemistry; Mice; Mice, SCID; Microscopy, Atomic Force; Peptides - chemistry; Rheology; Xenograft Model Antitumor Assays; doxorubicin; combination treatment; head and neck cancer; self-assembling peptide hydrogel; curcumin
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.8b01221

Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug’s aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with μCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.