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

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

Journal

Pharmaceutics
ISSN: 1999-4923

Output data

Year: 2023, Volume: 15, Article number : 2184, Pages count : DOI: 10.3390/pharmaceutics15092184

Tags

immunostimulatory RNA; cationic liposomes; lipoconjugates; cytokine-inducing activity; antitumor activity; IFN alpha

Authors

Bishani А. ¹ , Makarova D.M. ² , Shmendel E.V. ² , Maslov M.A. ² , Sen'kova A.V. ¹ , Savin I.A. ¹ , Gladkikh D.V. ¹ , Zenkova M.A. ¹ , Chernolovskaya E.L. ¹

Affiliations

1	Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva Ave. 8, 630090 Novosibirsk, Russia
2	Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, Vernadsky Ave. 86, 119571 Moscow, Russia

: 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.

Bishani А. , Makarova D.M. , Shmendel E.V. , Maslov M.A. , Sen'kova A.V. , Savin I.A. , Gladkikh D.V. , Zenkova M.A. , Chernolovskaya E.L.
Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA
Pharmaceutics. 2023. V.15. 2184 . DOI: 10.3390/pharmaceutics15092184 WOS Scopus PMID OpenAlex

Published print:

Aug 23, 2023

Web of science:	WOS:001072244100001
Scopus:	2-s2.0-85172453730
PMID:	37765155
OpenAlex:	W4386098950

DB	Citing
Scopus	2
OpenAlex	4
Web of science	3