Uncharged Gemini-Amphiphiles as Components of Cationic Liposomes for Delivery of Nucleic Acids

Shmendel, Elena V.; Bakhareva, S. A.; Makarova, D.; Chernikov, Ivan V.; Морозова, Н. Г.; Chernolovskaya, E. L.; Зенкова, М. А.; Маслов, М. А.

doi:10.1134/s106816202006031x

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…The delivery systems consist 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) (liposomes 2X3-DOPE), which were proven to effectively deliver various nucleic acids both in vitro and in vivo [ 22 , 23 ]. PEG-containing lipoconjugates with a loop-like structure have recently been synthesized, and we showed that the equipment of the liposomes with compounds having long oligoethylene hydrophilic spacers increases the efficiency of the TNAs delivery into cells as compared to Lipofectamine 3000 [ 24 ]. Here we describe the synthesis of several novel polyethylene glycol (PEG)-containing loop-like lipoconjugates differing in their molecular weight of PEG (800, 1500 and 2000 Da) and provide a detailed comparison of liposomes containing these lipoconjugates with PEG- and folate-lipoconjugates previously described [ 25 , 26 ] in liposome-mediated isRNA delivery in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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

Bishani,

Makarova,

Shmendel

et al. 2023

Pharmaceutics

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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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