Novel PEGylated Liposomes Enhance Immunostimulating Activity of IsRNA

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Nov 30

PMID 30486442

Citations 10

Authors

Tatyana Kabilova

Elena Shmendel

Daniil Gladkikh

Nina Morozova

Mikhail Maslov

Elena Chernolovskaya

Valentin Vlassov

Marina Zenkova

Affiliations

Soon will be listed here.

Abstract

The performance of cationic liposomes for delivery of therapeutic nucleic acids in vivo can be improved and specifically tailored to certain types of cargo and target cells by incorporation of PEG-containing lipoconjugates in the cationic liposome's composition. Here, we report on the synthesis of novel PEG-containing lipoconjugates with molecular masses of PEG 800, 1500 and 2000 Da. PEG-containing lipoconjugates were used as one of the components in liposome preparation with the polycationic amphiphile 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetra-azahexacosan tetrahydrochloride (2X3) and the lipid-helper dioleoylphosphatidylethanolamine (DOPE). We demonstrate that increasing the length of the PEG chain reduces the transfection activity of liposomes in vitro, but improves the biodistribution, increases the circulation time in the bloodstream and enhances the interferon-inducing activity of immunostimulating RNA in vivo.

Citing Articles

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References

Bellon L . Oligoribonucleotides with 2'-O-(tert-butyldimethylsilyl) groups. Curr Protoc Nucleic Acid Chem. 2008; Chapter 3:Unit 3.6. DOI: 10.1002/0471142700.nc0306s01. View

Xu H, Ye F, Hu M, Yin P, Zhang W, Li Y . Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection. Drug Deliv. 2014; 22(5):598-607. DOI: 10.3109/10717544.2014.885998. View

Singha K, Namgung R, Kim W . Polymers in small-interfering RNA delivery. Nucleic Acid Ther. 2011; 21(3):133-47. PMC: 3198620. DOI: 10.1089/nat.2011.0293. View

Kabilova T, Kovtonyuk L, Zonov E, Ryabchikova E, Popova N, Nikolin V . Immunotherapy of hepatocellular carcinoma with small double-stranded RNA. BMC Cancer. 2014; 14:338. PMC: 4038722. DOI: 10.1186/1471-2407-14-338. View

Petrova N, Chernikov I, Meschaninova M, Dovydenko I, Venyaminova A, Zenkova M . Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group. Nucleic Acids Res. 2011; 40(5):2330-44. PMC: 3299988. DOI: 10.1093/nar/gkr1002. View

Liu Y, Hu Y, Huang L . Influence of polyethylene glycol density and surface lipid on pharmacokinetics and biodistribution of lipid-calcium-phosphate nanoparticles. Biomaterials. 2014; 35(9):3027-34. PMC: 3926205. DOI: 10.1016/j.biomaterials.2013.12.022. View

Wolfrum C, Shi S, Narayanannair Jayaprakash K, Jayaraman M, Wang G, Pandey R . Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol. 2007; 25(10):1149-57. DOI: 10.1038/nbt1339. View

Wang C, Cheng X, Su Y, Pei Y, Song Y, Jiao J . Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs. Int J Nanomedicine. 2015; 10:3533-45. PMC: 4437610. DOI: 10.2147/IJN.S82481. View

Mosqueira V, Legrand P, Gref R, Heurtault B, Appel M, Barratt G . Interactions between a macrophage cell line (J774A1) and surface-modified poly (D,L-lactide) nanocapsules bearing poly(ethylene glycol). J Drug Target. 1999; 7(1):65-78. DOI: 10.3109/10611869909085493. View

10.

Bozzuto G, Molinari A . Liposomes as nanomedical devices. Int J Nanomedicine. 2015; 10:975-99. PMC: 4324542. DOI: 10.2147/IJN.S68861. View

11.

Klibanov A, Maruyama K, Torchilin V, Huang L . Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990; 268(1):235-7. DOI: 10.1016/0014-5793(90)81016-h. View

12.

Kabilova T, Senkova A, Nikolin V, Popova N, Zenkova M, Vlassov V . Antitumor and Antimetastatic Effect of Small Immunostimulatory RNA against B16 Melanoma in Mice. PLoS One. 2016; 11(3):e0150751. PMC: 4794162. DOI: 10.1371/journal.pone.0150751. View

13.

Maslov M, Kabilova T, Petukhov I, Morozova N, Serebrennikova G, Vlassov V . Novel cholesterol spermine conjugates provide efficient cellular delivery of plasmid DNA and small interfering RNA. J Control Release. 2011; 160(2):182-93. DOI: 10.1016/j.jconrel.2011.11.023. View

14.

Kabilova T, Shmendel E, Gladkikh D, Chernolovskaya E, Markov O, Morozova N . Targeted delivery of nucleic acids into xenograft tumors mediated by novel folate-equipped liposomes. Eur J Pharm Biopharm. 2017; 123:59-70. DOI: 10.1016/j.ejpb.2017.11.010. View

15.

Tagalakis A, Kenny G, Bienemann A, McCarthy D, Munye M, Taylor H . PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes. J Control Release. 2013; 174:177-87. DOI: 10.1016/j.jconrel.2013.11.014. View

16.

Kranz L, Diken M, Haas H, Kreiter S, Loquai C, Reuter K . Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 2016; 534(7607):396-401. DOI: 10.1038/nature18300. View

17.

Hashimoto Y, Lila A, Shimizu T, Ishida T, Kiwada H . B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG IgM production following injection of siRNA-containing PEGylated lipoplex in mice. J Control Release. 2014; 184:1-8. DOI: 10.1016/j.jconrel.2014.04.003. View

18.

Tagami T, Suzuki T, Matsunaga M, Nakamura K, Moriyoshi N, Ishida T . Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery. Int J Pharm. 2011; 422(1-2):280-9. DOI: 10.1016/j.ijpharm.2011.10.059. View

19.

Markov O, Mironova N, Maslov M, Petukhov I, Morozova N, Vlassov V . Novel cationic liposomes provide highly efficient delivery of DNA and RNA into dendritic cell progenitors and their immature offsets. J Control Release. 2011; 160(2):200-10. DOI: 10.1016/j.jconrel.2011.11.034. View

20.

Kierstead P, Okochi H, Venditto V, Chuong T, Kivimae S, Frechet J . The effect of polymer backbone chemistry on the induction of the accelerated blood clearance in polymer modified liposomes. J Control Release. 2015; 213:1-9. PMC: 4684485. DOI: 10.1016/j.jconrel.2015.06.023. View