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Article

Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia
2
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
3
D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
4
Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Gene L. Bidwell
Pharmaceutics 2021, 13(9), 1413; https://doi.org/10.3390/pharmaceutics13091413
Received: 31 July 2021 / Revised: 30 August 2021 / Accepted: 1 September 2021 / Published: 7 September 2021
Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. The aim of the study was to fabricate Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) variant DR5-B and to evaluate their in vitro cytotoxicity in 3D tumor spheroids. The Amph-PVP nanoparticles were obtained from a 1:1 mixture of unmodified and maleimide-modified polymeric chains, while DR5-B protein was modified by cysteine residue at the N-end for covalent conjugation with Amph-PVP. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. The cytotoxicity of the nanoparticles was investigated in human cell lines, namely breast adenocarcinoma MCF-7 and colorectal carcinomas HCT116 and HT29. Notably, DR5-B conjugation with Amph-PVP nanoparticles sensitized resistant multicellular tumor spheroids from MCF-7 and HT29 cells. Taking into account the nanoparticles loading ability with a wide range of low-molecular-weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, we suggest further development to obtain a versatile system for targeted drug delivery into tumor cells. View Full-Text
Keywords: poly(N-vinylpyrrolidone); self-assembly; nanoparticles; targeted drug delivery system; DR5 receptor; TRAIL variant DR5-B; multicellular tumor spheroids; antitumor therapy poly(N-vinylpyrrolidone); self-assembly; nanoparticles; targeted drug delivery system; DR5 receptor; TRAIL variant DR5-B; multicellular tumor spheroids; antitumor therapy
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MDPI and ACS Style

Yagolovich, A.; Kuskov, A.; Kulikov, P.; Kurbanova, L.; Bagrov, D.; Artykov, A.; Gasparian, M.; Sizova, S.; Oleinikov, V.; Gileva, A.; Kirpichnikov, M.; Dolgikh, D.; Markvicheva, E. Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells. Pharmaceutics 2021, 13, 1413. https://doi.org/10.3390/pharmaceutics13091413

AMA Style

Yagolovich A, Kuskov A, Kulikov P, Kurbanova L, Bagrov D, Artykov A, Gasparian M, Sizova S, Oleinikov V, Gileva A, Kirpichnikov M, Dolgikh D, Markvicheva E. Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells. Pharmaceutics. 2021; 13(9):1413. https://doi.org/10.3390/pharmaceutics13091413

Chicago/Turabian Style

Yagolovich, Anne, Andrey Kuskov, Pavel Kulikov, Leily Kurbanova, Dmitry Bagrov, Artem Artykov, Marine Gasparian, Svetlana Sizova, Vladimir Oleinikov, Anastasia Gileva, Mikhail Kirpichnikov, Dmitry Dolgikh, and Elena Markvicheva. 2021. "Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells" Pharmaceutics 13, no. 9: 1413. https://doi.org/10.3390/pharmaceutics13091413

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