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Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA

In this study, the impact of different delivery systems on the cytokine-inducing, antiproliferative, and antitumor activities of short immunostimulatory double-stranded RNA (isRNA) was investigated. The delivery systems, consisting of the polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonyl...

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Autores principales: Bishani, Ali, Makarova, Darya M., Shmendel, Elena V., Maslov, Mikhail A., Sen‘kova, Aleksandra V., Savin, Innokenty A., Gladkikh, Daniil V., Zenkova, Marina A., Chernolovskaya, Elena L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535620/
https://www.ncbi.nlm.nih.gov/pubmed/37765155
http://dx.doi.org/10.3390/pharmaceutics15092184
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author Bishani, Ali
Makarova, Darya M.
Shmendel, Elena V.
Maslov, Mikhail A.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Gladkikh, Daniil V.
Zenkova, Marina A.
Chernolovskaya, Elena L.
author_facet Bishani, Ali
Makarova, Darya M.
Shmendel, Elena V.
Maslov, Mikhail A.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Gladkikh, Daniil V.
Zenkova, Marina A.
Chernolovskaya, Elena L.
author_sort Bishani, Ali
collection PubMed
description In this study, the impact of different delivery systems on the cytokine-inducing, antiproliferative, and antitumor activities of short immunostimulatory double-stranded RNA (isRNA) was investigated. The delivery systems, consisting of the polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20 tetraazahexacosan tetrahydrochloride (2X3), and the lipid-helper dioleoylphosphatidylethanolamine (DOPE), were equipped with polyethylene glycol lipoconjugates differing in molecular weight and structure. The main findings of this work are as follows: (i) significant activation of MCP-1 and INF-α, β, and γ production in CBA mice occurs under the action of isRNA complexes with liposomes containing lipoconjugates with long PEG chains, while activation of MCP-1 and INF-γ, but not INF-α or β, was observed under the action of isRNA lipoplexes containing lipoconjugates with short PEG chains; (ii) a pronounced antiproliferative effect on B16 melanoma cells in vitro, as well as an antitumor and hepatoprotective effect in vivo, was induced by isRNA pre-complexes with non-pegylated liposomes, while complexes containing lipoconjugates with long-chain liposomes were inactive; (iii) the antitumor activity of isRNA correlated with the efficiency of its accumulation in the cells and did not explicitly depend on the activation of cytokine and interferon production. Thus, the structure of the delivery system plays a vital role in determining the response to isRNA and allows for the choice of a delivery system depending on the desired effect.
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spelling pubmed-105356202023-09-29 Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA Bishani, Ali Makarova, Darya M. Shmendel, Elena V. Maslov, Mikhail A. Sen‘kova, Aleksandra V. Savin, Innokenty A. Gladkikh, Daniil V. Zenkova, Marina A. Chernolovskaya, Elena L. Pharmaceutics Article In this study, the impact of different delivery systems on the cytokine-inducing, antiproliferative, and antitumor activities of short immunostimulatory double-stranded RNA (isRNA) was investigated. The delivery systems, consisting of the polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20 tetraazahexacosan tetrahydrochloride (2X3), and the lipid-helper dioleoylphosphatidylethanolamine (DOPE), were equipped with polyethylene glycol lipoconjugates differing in molecular weight and structure. The main findings of this work are as follows: (i) significant activation of MCP-1 and INF-α, β, and γ production in CBA mice occurs under the action of isRNA complexes with liposomes containing lipoconjugates with long PEG chains, while activation of MCP-1 and INF-γ, but not INF-α or β, was observed under the action of isRNA lipoplexes containing lipoconjugates with short PEG chains; (ii) a pronounced antiproliferative effect on B16 melanoma cells in vitro, as well as an antitumor and hepatoprotective effect in vivo, was induced by isRNA pre-complexes with non-pegylated liposomes, while complexes containing lipoconjugates with long-chain liposomes were inactive; (iii) the antitumor activity of isRNA correlated with the efficiency of its accumulation in the cells and did not explicitly depend on the activation of cytokine and interferon production. Thus, the structure of the delivery system plays a vital role in determining the response to isRNA and allows for the choice of a delivery system depending on the desired effect. MDPI 2023-08-23 /pmc/articles/PMC10535620/ /pubmed/37765155 http://dx.doi.org/10.3390/pharmaceutics15092184 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bishani, Ali
Makarova, Darya M.
Shmendel, Elena V.
Maslov, Mikhail A.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Gladkikh, Daniil V.
Zenkova, Marina A.
Chernolovskaya, Elena L.
Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title_full Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title_fullStr Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title_full_unstemmed Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title_short Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
title_sort influence of the composition of cationic liposomes on the performance of cargo immunostimulatory rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535620/
https://www.ncbi.nlm.nih.gov/pubmed/37765155
http://dx.doi.org/10.3390/pharmaceutics15092184
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