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

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Abstract

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.

About the authors

Anastasia M. Gileva

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS; Mendeleev Russian University of Chemical Technology

Email: sumina.anastasia@mail.ru
ORCID iD: 0000-0001-8220-0580
SPIN-code: 3401-5241

junior researcher

Russian Federation, Moscow; Moscow

Daria I. Kulikova

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS; Mendeleev Russian University of Chemical Technology

Email: dkulikovaaa@mail.ru
Russian Federation, Moscow; Moscow

Ekaterina V. Kukovyakina

Mendeleev Russian University of Chemical Technology

Email: kev0700@yandex.ru
ORCID iD: 0009-0008-2918-185X
SPIN-code: 9172-4087
Russian Federation, Moscow

Anne V. Yagolovich

Lomonosov Moscow State University

Email: anne-gor2002@yandex.ru
ORCID iD: 0000-0003-3145-3726
SPIN-code: 2076-1814

Cand. Sci. (Biology)

Russian Federation, Moscow

Kirill S. Kushnerev

Mendeleev Russian University of Chemical Technology

Email: firstavenue@mail.ru
ORCID iD: 0000-0003-2866-9796
SPIN-code: 4968-0941
Russian Federation, Moscow

Andrey N. Kuskov

Mendeleev Russian University of Chemical Technology

Email: kuskov.a.n@muctr.ru
ORCID iD: 0000-0001-8140-2754
SPIN-code: 6115-8494
ResearcherId: R-7314-2016

Dr. Sci. (Chemistry), Professor 

Russian Federation, Moscow

Elena A. Markvicheva

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS

Author for correspondence.
Email: lemarkv@hotmail.com
ORCID iD: 0000-0001-6652-3267

Dr. Sci. (Chemistry)

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Synthesis of amphiphilic derivatives of poly-N-vinylpyrrolidone for subsequent production of modified polymeric nanoparticles with curcumin.

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3. Fig. 2. In vitro release profiles of curcumin from the Amph-PVP-Cur and Amph-PVP-AK-Mal-Cur nanoparticles. Free curcumin was used as a control.

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4. Fig. 3. Accumulation efficiency of the polymeric nanoparticles loaded with curcumin in monolayer culture (2D in vitro model) and tumor spheroids (3D in vitro model) from human ovarian adenocarcinoma OVCAR-3 cells Flow cytometry (2D in vitro model) and fluorimetry (3D in vitro model). **** p <0.001.

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5. Fig. 4. Cytotoxicity of the polymeric nanoparticles in monolayer culture (2D in vitro model) and in tumor spheroids (3D in vitro model) from human ovarian adenocarcinoma OVCAR-3 cells after incubation for 24 and 48 h. MTT-test.

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