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

Abstract

IntroductionTo investigate the toxicity of combretastatin A4 phosphate (CA4P) hyaluronic acid (HA) gel nanoparticles (HA-CA4P-NPs) in OSCC (oral squamous cell carcinoma).MethodsToxicity was investigated using fluorescence microscopy, MTT as-say, flow cytometry, and OSCC xenograft mouse models.ResultsCompared 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.ConclusionsHA-CA4P-NPs improved drug release and delivery, and in-creased cytotoxicity to cancer cells.