Molecular Pharmaceutics, volume 18, issue 1, pages 461-468

New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma

Petrov Rostislav A ^{1, 2}

Mefedova Sofiia R ²

Yamansarov Emil Yu ^{2, 3}

Maklakova Svetlana ^{2, 3}

Grishin Dmitrii A ²

Lopatukhina Elena V. ²

Burenina Olga Y ⁴

Lopukhov Anton V ²

Kovalev Sergey ²

Timchenko Yury V ²

Ondar Evgenia E ²

Ivanenkov Yan ^{1, 5}

Evteev Sergei A ²

Vaneev Alexander N. ^{2, 3}

Timoshenko Roman V ³

Klyachko Natalia L. ^{2, 4}

Erofeev Alexander V. ^{2, 3}

Gorelkin Peter ^{2, 3}

Beloglazkina Elena K. ²

Majouga Alexander G. ^{2, 3, 6}

Hide authors affiliations Show authors affiliations: 6 affiliations

Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) of the Ufa Federal Research Centre, Oktyabrya Prospekt 71, Ufa 450054, Russian Federation

Institute of Biochemistry and Genetics of the Ufa Federal Research Center of the Russian Academy of Sciences

Ufa Federal Research Center of the Russian Academy of Sciences

Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation |

National University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian Federation |

⁴

Skolkovo Institute of Science and Technology, 3 Nobel str., Skolkovo 143026, Russian Federation |

⁵

Moscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, Dolgoprudny City, Moscow 141700, Russian Federation |

⁶

Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian Federation |

Publication type: Journal Article

Publication date: 2020-12-02

American Chemical Society (ACS)

Journal: Molecular Pharmaceutics

Quartile SCImago

Quartile WOS

Impact factor: 4.9

ISSN: 15438384, 15438392

DOI: 10.1021/acs.molpharmaceut.0c00980

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Drug Discovery

Pharmaceutical Science

Molecular Medicine

Abstract

In this work, we have developed covalent and low molecular weight docetaxel delivery systems based on conjugation with N-acetyl-d-galactosamine and studied their properties related to hepatocellular carcinoma cells. The resulting glycoconjugates have an excellent affinity to the asialoglycoprotein receptor (ASGPR) in the nanomolar range of concentrations and a high cytotoxicity level comparable to docetaxel. Likewise, we observed the 21-75-fold increase in water solubility in comparison with parent docetaxel and prodrug lability to intracellular conditions with half-life values from 25.5 to 42 h. We also found that the trivalent conjugate possessed selective toxicity against hepatoma cells vs control cell lines (20-35 times). The absence of such selectivity in the case of monovalent conjugates indicates the effect of ligand valency. Specific ASGPR-mediated cellular uptake of conjugates was proved in vitro using fluorescent-labeled analogues. In addition, we showed an enhanced generation of reactive oxygen species in the HepG2 cells, which could be inhibited by the natural ligand of ASGPR. Overall, the obtained results highlight the potential of ASGPR-directed cytostatic taxane drugs for selective therapy of hepatocellular carcinoma.

By date By citations

Citations by journals

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Russian Journal of Organic Chemistry	Russian Journal of Organic Chemistry, 2, 9.52% Russian Journal of Organic Chemistry 2 publications, 9.52%
Inorganic Chemistry Frontiers	Inorganic Chemistry Frontiers, 1, 4.76% Inorganic Chemistry Frontiers 1 publication, 4.76%
RSC Medicinal Chemistry	RSC Medicinal Chemistry, 1, 4.76% RSC Medicinal Chemistry 1 publication, 4.76%
Journal of Nanobiotechnology	Journal of Nanobiotechnology, 1, 4.76% Journal of Nanobiotechnology 1 publication, 4.76%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 4.76% International Journal of Molecular Sciences 1 publication, 4.76%
Journal of Cluster Science	Journal of Cluster Science, 1, 4.76% Journal of Cluster Science 1 publication, 4.76%
Molecular Pharmaceutics	Molecular Pharmaceutics, 1, 4.76% Molecular Pharmaceutics 1 publication, 4.76%
Journal of Medicinal Chemistry	Journal of Medicinal Chemistry, 1, 4.76% Journal of Medicinal Chemistry 1 publication, 4.76%
European Journal of Organic Chemistry	European Journal of Organic Chemistry, 1, 4.76% European Journal of Organic Chemistry 1 publication, 4.76%
Advanced healthcare materials	Advanced healthcare materials, 1, 4.76% Advanced healthcare materials 1 publication, 4.76%
Molecules	Molecules, 1, 4.76% Molecules 1 publication, 4.76%
International Journal of Nanomedicine	International Journal of Nanomedicine, 1, 4.76% International Journal of Nanomedicine 1 publication, 4.76%
Molecular Therapy - Nucleic Acids	Molecular Therapy - Nucleic Acids, 1, 4.76% Molecular Therapy - Nucleic Acids 1 publication, 4.76%
SSRN Electronic Journal	SSRN Electronic Journal, 1, 4.76% SSRN Electronic Journal 1 publication, 4.76%
Cells	Cells, 1, 4.76% Cells 1 publication, 4.76%
Moscow University Chemistry Bulletin	Moscow University Chemistry Bulletin, 1, 4.76% Moscow University Chemistry Bulletin 1 publication, 4.76%
Lomonosov chemistry journal	Lomonosov chemistry journal, 1, 4.76% Lomonosov chemistry journal 1 publication, 4.76%
Colloid Journal	Colloid Journal, 1, 4.76% Colloid Journal 1 publication, 4.76%
Analytical Chemistry	Analytical Chemistry, 1, 4.76% Analytical Chemistry 1 publication, 4.76%
Science China Life Sciences	Science China Life Sciences, 1, 4.76% Science China Life Sciences 1 publication, 4.76%
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Citations by publishers

	1 2 3 4
Pleiades Publishing	Pleiades Publishing, 4, 19.05% Pleiades Publishing 4 publications, 19.05%
Springer Nature	Springer Nature, 3, 14.29% Springer Nature 3 publications, 14.29%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 3, 14.29% Multidisciplinary Digital Publishing Institute (MDPI) 3 publications, 14.29%
American Chemical Society (ACS)	American Chemical Society (ACS), 3, 14.29% American Chemical Society (ACS) 3 publications, 14.29%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 2, 9.52% Royal Society of Chemistry (RSC) 2 publications, 9.52%
Wiley	Wiley, 2, 9.52% Wiley 2 publications, 9.52%
Dove Medical Press	Dove Medical Press, 1, 4.76% Dove Medical Press 1 publication, 4.76%
Elsevier	Elsevier, 1, 4.76% Elsevier 1 publication, 4.76%
Social Science Electronic Publishing	Social Science Electronic Publishing, 1, 4.76% Social Science Electronic Publishing 1 publication, 4.76%
Moscow University Press	Moscow University Press, 1, 4.76% Moscow University Press 1 publication, 4.76%
	1 2 3 4

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Petrov R. A. et al. New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma // Molecular Pharmaceutics. 2020. Vol. 18. No. 1. pp. 461-468.

GOST all authors (up to 50) Copy

Petrov R. A., Mefedova S. R., Yamansarov E. Yu., Maklakova S., Grishin D. A., Lopatukhina E. V., Burenina O. Y., Lopukhov A. V., Kovalev S., Timchenko Y. V., Ondar E. E., Ivanenkov Y., Evteev S. A., Vaneev A. N., Timoshenko R. V., Klyachko N. L., Erofeev A. V., Gorelkin P., Beloglazkina E. K., Majouga A. G. New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma // Molecular Pharmaceutics. 2020. Vol. 18. No. 1. pp. 461-468.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1021/acs.molpharmaceut.0c00980

UR - https://doi.org/10.1021%2Facs.molpharmaceut.0c00980

TI - New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma

T2 - Molecular Pharmaceutics

AU - Mefedova, Sofiia R

AU - Grishin, Dmitrii A

AU - Lopatukhina, Elena V.

AU - Ondar, Evgenia E

AU - Timoshenko, Roman V

AU - Evteev, Sergei A

AU - Petrov, Rostislav A

AU - Yamansarov, Emil Yu

AU - Maklakova, Svetlana

AU - Lopukhov, Anton V

AU - Kovalev, Sergey

AU - Ivanenkov, Yan

AU - Vaneev, Alexander N.

AU - Klyachko, Natalia L.

AU - Majouga, Alexander G.

AU - Burenina, Olga Y

AU - Timchenko, Yury V

AU - Erofeev, Alexander V.

AU - Gorelkin, Peter

AU - Beloglazkina, Elena K.

PY - 2020

DA - 2020/12/02 00:00:00

PB - American Chemical Society (ACS)

SP - 461-468

IS - 1

VL - 18

SN - 1543-8384

SN - 1543-8392

ER -

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BibTex Copy

@article{2020_Petrov,

author = {Sofiia R Mefedova and Dmitrii A Grishin and Elena V. Lopatukhina and Evgenia E Ondar and Roman V Timoshenko and Sergei A Evteev and Rostislav A Petrov and Emil Yu Yamansarov and Svetlana Maklakova and Anton V Lopukhov and Sergey Kovalev and Yan Ivanenkov and Alexander N. Vaneev and Natalia L. Klyachko and Alexander G. Majouga and Olga Y Burenina and Yury V Timchenko and Alexander V. Erofeev and Peter Gorelkin and Elena K. Beloglazkina},

title = {New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma},

journal = {Molecular Pharmaceutics},

year = {2020},

volume = {18},

publisher = {American Chemical Society (ACS)},

month = {dec},

url = {https://doi.org/10.1021%2Facs.molpharmaceut.0c00980},

number = {1},

pages = {461--468},

doi = {10.1021/acs.molpharmaceut.0c00980}

}

MLA

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MLA Copy

Petrov, Rostislav A., et al. “New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma.” Molecular Pharmaceutics, vol. 18, no. 1, Dec. 2020, pp. 461-468. https://doi.org/10.1021%2Facs.molpharmaceut.0c00980.

Found error?

Publisher

American Chemical Society (ACS)

Journal

Molecular Pharmaceutics

Quartile SCImago

Quartile WOS

Impact factor

4.9

ISSN

15438384 (Print)
15438392 (Electronic)

Labs

Laboratory of Biologically Active Organic Compounds (BAOС)

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