Cytotoxicity of curcumin-loaded nanoparticles based on amphiphilic poly-N-vinylpyrrolidone derivatives in 2D and 3D <i>in vitro</i> models of human ovarian adenocarcinoma

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BACKGROUND: Nanocarriers based on biocompatible polymers are a promising delivery tool for biologically active substances and drugs, in particular antitumor agents. Curcumin, a polyphenol, is known to possess pleiotropic therapeutic effects, including antitumor activity. The antitumor potential of curcumin has been shown in various tumor types, including ovarian adenocarcinoma. However, its lipophilic properties and very low bioavailability limits its use. Incorporating curcumin into nanocarriers enhances its delivery options and expands its potential as an antitumor agent. AIM: To produce curcumin-loaded polymeric nanoparticles based on amphiphilic poly-N-vinylpyrrolidone derivatives and its copolymers with acrylic acid, explore their accumulation in the tumor cells; evaluate in vitro cytotoxicity in 2D (monolayer cell culture) and 3D (tumor spheroids) models of human ovarian adenocarcinoma. MATERIALS AND METHODS: The polymers of the amphiphilic poly-N-vinylpyrrolidone derivatives and its copolymers with acrylic acid were obtained using radical polymerization. Emulsion method was used to obtain polymeric nanoparticles. Accumulation of nanoparticles in tumor cells was assessed using flow cytometry (for monolayer culture) or fluorimetric analysis (for spheroids). Cytotoxicity was studied in 2D and 3D models obtained of the human ovarian adenocarcinoma cell line OVCAR-3 using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay). RESULTS: The effective accumulation of curcumin-loaded polymeric nanoparticles in both monolayer culture cells and tumor spheroids was demonstrated. Curcumin-loaded nanoparticles exhibited high-level cytotoxicity in the 2D model of human ovarian adenocarcinoma cells OVCAR-3 (IC50 up to 137±9 μg/mL) and a moderate, although significant cytotoxic effect in a 3D in vitro model. Meanwhile, nanoparticles not loaded with curcumin did not show any cytotoxic activity regardless of their composition or of the additional modification, i.e. with the use of maleimide functional groups. CONCLUSION: These data can provide a foundation for further studies to assess the safety and in vivo antitumor activity of curcumin-loaded nanoparticles based on amphiphilic poly-N-vinylpyrrolidone derivatives.