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Abstract

Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids †

by
Anne Yagolovich
1,*,
Andrey Kuskov
2,
Pavel Kulikov
3,
Leily Kurbanova
1,
Anastasia Gileva
1 and
Elena Markvicheva
1
1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia
2
Department of Biomaterials, Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
3
Center of Strategic Planning and Management of Medical and Biological Health Risks, 119121 Moscow, Russia
*
Author to whom correspondence should be addressed.
†
Presented at the 2nd International Online Conference on Polymer Science—Polymers and Nanotechnology for Industry 4.0, 1–15 November 2021; Available online: https://iocps2021.sciforum.net/.
Mater. Proc. 2021, 7(1), 8; https://doi.org/10.3390/IOCPS2021-11281
Published: 1 November 2021
(This article belongs to the Proceedings of The 2nd International Online Conference on Polymer Science—Polymers and Nanotechnology for Industry 4.0)
Versions Notes

Abstract

:
Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were proposed earlier as a new drug delivery system. In the current work, we study the antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with the antitumor receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP polymer was synthesized by the earlier developed one-step technique (Kulikov et al., Polym. Sci. Ser. D, 2017). To stabilize Amph-PVP associates, the hydrophobic core was loaded with the model substance prothionamide. For the covalent conjugation with DR5-B, the hydrophilic ends of polymeric chains were modified with maleimide, and a DR5-B N-terminal amino acid residue valine was mutated to cysteine (DR5-B/V114C). DR5-B/V114C was conjugated to the surface of polymeric micelles by the selective covalent interaction of N-terminal cysteine residue with maleimide on Amph-PVP. The cytotoxicity of DR5-B-conjugated Amph-PVP polymeric nanoparticles was investigated in 3D multicellular tumor spheroids (MCTS) of human colon carcinoma HCT116 and HT29 cells, generated by the RGD-induced self-assembly technique (Akasov et al., Int. J. Pharm., 2016). In DR5-B-sensitive HCT116 MCTS, the P-DR5-B activity slightly increased compared to that of DR5-B. However, in DR5-B-resistant HT29 MCTS, P-DR5-B significantly surpassed DR5-B in the antitumor activity. Thus, the conjugation of DR5-B with the Amph-PVP nanoparticles enhanced its tumor-cell killing capacity. In the current study, we obtain a new nano-scaled delivery system based on Amph-PVP self-aggregates coated with covalently conjugated antitumor DR5-specific cytokine DR5-B. P-DR5-B overcomes DR5-B-resistance of the human colon carcinoma MCTS in vitro. This makes Amph-PVP polymeric nanoparticles a prospective and versatile nano-scaled delivery system for the targeted proteins.

Supplementary Materials

The poster presentation is available online at https://www.mdpi.com/article/10.3390/IOCPS2021-11281/s1.

Author Contributions

Conceptualization, A.Y. and A.K.; methodology, A.Y., A.K. and E.M.; validation, A.Y. and A.G.; formal analysis, A.Y., A.K., A.G. and E.M.; investigation, P.K. and L.K.; resources, A.K. and E.M.; data curation, A.Y. and A.G.; writing—original draft preparation, A.Y. and P.K.; writing—review and editing, A.K. and E.M.; visualization, A.Y., P.K. and A.G.; supervision, E.M.; project administration, A.Y. and E.M.; funding acquisition, A.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Russian Science Foundation grant No. 21-14-00224, https://rscf.ru/project/21-14-00224/ (protein expression and purification and development of 3D tumor models were held at Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences) and by the Russian Foundation for Basic Research grant № 18-34-00812 (nanoparticle synthesis and characterization were held at Department of Biomaterials, D. Mendeleev University of Chemical Technology of Russia and Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, Moscow, Russia).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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MDPI and ACS Style

Yagolovich, A.; Kuskov, A.; Kulikov, P.; Kurbanova, L.; Gileva, A.; Markvicheva, E. Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids. Mater. Proc. 2021, 7, 8. https://doi.org/10.3390/IOCPS2021-11281

AMA Style

Yagolovich A, Kuskov A, Kulikov P, Kurbanova L, Gileva A, Markvicheva E. Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids. Materials Proceedings. 2021; 7(1):8. https://doi.org/10.3390/IOCPS2021-11281

Chicago/Turabian Style

Yagolovich, Anne, Andrey Kuskov, Pavel Kulikov, Leily Kurbanova, Anastasia Gileva, and Elena Markvicheva. 2021. "Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids" Materials Proceedings 7, no. 1: 8. https://doi.org/10.3390/IOCPS2021-11281

APA Style

Yagolovich, A., Kuskov, A., Kulikov, P., Kurbanova, L., Gileva, A., & Markvicheva, E. (2021). Antitumor Cytokine DR5-B-Conjugated Polymeric Poly(N-vinylpyrrolidone) Nanoparticles with Enhanced Cytotoxicity in Human Colon Carcinoma 3D Cell Spheroids. Materials Proceedings, 7(1), 8. https://doi.org/10.3390/IOCPS2021-11281

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