Polymer-ritonavir derivate nanomedicine with pH-sensitive activation possesses potent anti-tumor activity in vivo via inhibition of proteasome and STAT3 signaling.

Antitumor activity Polymer carrier Proteasome inhibition Ritonavir derivate STAT3 signaling inhibition pH-controlled release

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 04 2021
Historique:
received: 11 11 2020
revised: 07 03 2021
accepted: 10 03 2021
pubmed: 17 3 2021
medline: 8 7 2021
entrez: 16 3 2021
Statut: ppublish

Résumé

Drug repurposing is a promising strategy for identifying new applications for approved drugs. Here, we describe a polymer biomaterial composed of the antiretroviral drug ritonavir derivative (5-methyl-4-oxohexanoic acid ritonavir ester; RD), covalently bound to HPMA copolymer carrier via a pH-sensitive hydrazone bond (P-RD). Apart from being more potent inhibitor of P-glycoprotein in comparison to ritonavir, we found RD to have considerable cytostatic activity in six mice (IC

Identifiants

pubmed: 33722611
pii: S0168-3659(21)00126-7
doi: 10.1016/j.jconrel.2021.03.015
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Polymers 0
Doxorubicin 80168379AG
Proteasome Endopeptidase Complex EC 3.4.25.1
Ritonavir O3J8G9O825

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

563-580

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Ladislav Sivák (L)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Vladimír Šubr (V)

Institute of Macromolecular Chemistry, Czech Academy of Sciences, v.v.i., Heyrovskeho nam. 2, 16206 Prague, Czech Republic.

Jiřina Kovářová (J)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Barbora Dvořáková (B)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Milada Šírová (M)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Blanka Říhová (B)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Eva Randárová (E)

Institute of Macromolecular Chemistry, Czech Academy of Sciences, v.v.i., Heyrovskeho nam. 2, 16206 Prague, Czech Republic.

Michal Kraus (M)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Jakub Tomala (J)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Martin Studenovský (M)

Institute of Macromolecular Chemistry, Czech Academy of Sciences, v.v.i., Heyrovskeho nam. 2, 16206 Prague, Czech Republic.

Michaela Vondráčková (M)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic.

Radislav Sedláček (R)

Czech Center of Phenogenomics, Institute of Molecular Genetics, Czech Academy of Sciences, v.v.i., Prumyslova 595, 25250 Vestec, Czech Republic.

Petr Makovický (P)

Czech Center of Phenogenomics, Institute of Molecular Genetics, Czech Academy of Sciences, v.v.i., Prumyslova 595, 25250 Vestec, Czech Republic.

Jitka Fučíková (J)

Department of Immunology, Charles University, 2(nd) Faculty of Medicine and University Hospital Motol, V uvalu 84, 15006 Prague, Czech Republic; Sotio, Jankovcova 1518, 17000 Prague, Czech Republic.

Šárka Vošáhlíková (Š)

Sotio, Jankovcova 1518, 17000 Prague, Czech Republic.

Radek Špíšek (R)

Department of Immunology, Charles University, 2(nd) Faculty of Medicine and University Hospital Motol, V uvalu 84, 15006 Prague, Czech Republic; Sotio, Jankovcova 1518, 17000 Prague, Czech Republic.

Libor Kostka (L)

Institute of Macromolecular Chemistry, Czech Academy of Sciences, v.v.i., Heyrovskeho nam. 2, 16206 Prague, Czech Republic.

Tomáš Etrych (T)

Institute of Macromolecular Chemistry, Czech Academy of Sciences, v.v.i., Heyrovskeho nam. 2, 16206 Prague, Czech Republic. Electronic address: etrych@imc.cas.cz.

Marek Kovář (M)

Institute of Microbiology, Czech Academy of Sciences, v.v.i., Videnska 1083, 14220 Prague, Czech Republic. Electronic address: makovar@biomed.cas.cz.

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Classifications MeSH