Combretastatin A4 phosphate encapsulated in hyaluronic acid nanoparticles is highly cytotoxic to oral squamous cell carcinoma

Abstract

Introduction To investigate the toxicity of combretastatin A4 phosphate (CA4P) hyaluronic acid (HA) gel nanoparticles (HA-CA4P-NPs) in OSCC (oral squamous cell carcinoma). Methods Toxicity was investigated using fluorescence microscopy, MTT as-say, flow cytometry, and OSCC xenograft mouse models. Results Compared with CA4P, HA-CA4P-NPs generated nearly 10 times more fluorescence in OSCC cells. Cytotoxicity assays showed that HACA4P-NPs were more toxic to SCC-4 cells but not to HNECs. Remarkable necrosis was induced in SCC-4 cells after exposure to HA-CA4P-NPs, and related proteins were upregulated. Furthermore, HA-CA4P-NPs significantly reduced the tu-mour size. Conclusions HA-CA4P-NPs improved drug release and delivery, and in-creased cytotoxicity to cancer cells.

Keywords

• oral squamous cell carcinoma
• targeted drug delivery
• combretastatin a4
• antitumour activity