Alginate-coated chitosan nanogels differentially modulate class-A and class-B CpG-ODN targeting of dendritic cells and intracellular delivery

• Published in: Nanomedicine Vol. 10; no. 8; pp. 1739 - 1749
• Main Authors: Démoulins, Thomas, PhD, Milona, Panagiota, PhD, McCullough, Kenneth C., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2014
• Subjects: Alginates - chemistry; Animals; Blood dendritic cell targeting; Cells, Cultured; Chitosan - chemistry; CpG-ODN; Dendritic Cells - metabolism; Flow Cytometry; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Humans; Internal Medicine; Intracellular delivery; Microscopy, Confocal; Nanoparticles; Oligodeoxyribonucleotides - chemistry; Swine; fluorescence-activated cell sorter; plasmacytoid dendritic cells PE, phycoerythrin; DLS; FACS; Nanoparticles; DMEM; MFI; FITC; dendritic cells; DCs; TPP; pDCs; Toll-like receptors; Ng; PAMPs; sodium triphosphate, pentabasic; TLR; fluorescein isothiocyanate; peripheral blood mononuclear cells; mean fluorescence intensity; Blood dendritic cell targeting; Intracellular delivery; PBMCs; Dulbecco's modified Eagle's medium; nanogel; pathogen-associated molecular patterns; conventional (also known as classical) dendritic cells; CpG oligodeoxynucleotide; enzyme-linked immunosorbent assay; CpG-ODN; Dynamic Light Scattering; cDCs; ELISA
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2014.06.003

Abstract CpG-oligodeoxynucleotides (CpG-ODNs) interact with dendritic cells (DCs), but evidence is less clear for CpG-ODN admixed with or incorporated into vaccine delivery vehicles. We loaded alginate-coated chitosan-nanogels (Ng) with class-A or class-B CpG-ODN, and compared with the same CpG-ODNs free or admixed with empty Ng. Experiments were performed on both porcine and human blood DC subpopulations. Encapsulation of class-A CpG-ODN (loading into Ng) strongly reduced the CpG-ODN uptake and intracellular trafficking in the cytosol; this was associated with a marked deficiency in IFN-α induction. In contrast, encapsulation of class-B CpG-ODN increased its uptake and did not influence consistently intracellular trafficking into the nucleus. The choice of CpG-ODN class as adjuvant is thus critical in terms of how it will behave with nanoparticulate vaccine delivery vehicles. The latter can have distinctive modulatory influences on the CpG-ODN, which would require definition for different CpG-ODN and delivery vehicles prior to vaccine formulation. From the Clinical Editor This basic science study investigates the role of class-A and class-B CpG-oligodeoxynucleotides loaded into alginate-coated chitosan nanogels, demonstrating differential effects between the two classes as related to the use of these nanoformulations as vaccine delivery vehicles.