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Description:

Cationic liposomes, specifically 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) liposomes, serve as successful carriers for guanine-quadruplex (G4) structure-based cytosine-guanine oligodeoxynucleotides (CpG ODNs). The combined benefits of CpG ODNs forming a G4 structure and a non-viral vector carrier endow the ensuing complex with promising adjuvant properties. Although G4-CpG ODN-DOTAP complexes show a higher immunostimulatory effect than naked G4-CpG ODNs, the effects of the complex composition, especially charge ratios, on the production of the pro-inflammatory cytokines interleukin (IL)-6 and interferon (IFN)-alpha remain unclear. Here, we examined whether charge ratios drive the bifurcation of cytokine inductions in human peripheral blood mononuclear cells. Linear CpG ODN-DOTAP liposome complexes formed micrometer-sized positively charged agglomerates; G4-CpG ODN-DOTAP liposome complexes with low charge ratios (0.5 and 1.5) formed ~250 nm-sized negatively charged complexes. Notably, low-charge-ratio (0.5 and 1.5) complexes induced significantly higher IL-6 and IFN-alpha levels simultaneously than high-charge-ratio (2 and 2.5) complexes. Moreover, confocal microscopy indicated a positive correlation between the cellular uptake of the complex and amount of cytokine induced. The observed effects of charge ratios on complex size, surface charge, and affinity for factors that modify cellular-uptake, intracellular-activity, and cytokine-production efficiency highlight the importance of a rational complex design for delivering and controlling G4-CpG ODN activity.

Rights:

• Creative Commons BY Attribution 4.0 International
  

Keyword: guanine quadruplex, CpG oligodeoxynucleotides, cationic liposomes, vaccine, immunotherapy, DNA delivery, liposome

Date published: 2023-11-11

Publisher: MDPI AG

Journal:

• Biomolecules (ISSN: 2218273X) vol. 13 issue. 11 1639

Funding:

• Japan Society for the Promotion of Science KAKENHI 17KK0122 (日本学術振興会)
• TIA collaborative research program “Kakehashi” TK21-017 (TIA 連携プログラム探索推進事業「かけはし」)
• TIA collaborative research program “Kakehashi” TK22-033 (TIA 連携プログラム探索推進事業「かけはし」)
• Japan Society for the Promotion of Science KAKENHI 21K19057 (日本学術振興会)

Manuscript type: Publisher's version (Version of record)

MDR DOI:

First published URL: https://doi.org/10.3390/biom13111639

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Updated at: 2024-04-30 12:30:21 +0900

Published on MDR: 2024-04-30 12:30:21 +0900