N-Oxy lipid-based click chemistry for orthogonal coupling of mannan onto nanoliposomes prepared by microfluidic mixing: Synthesis of lipids, characterisation of mannan-coated nanoliposomes and in vitro stimulation of dendritic cells
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
30600036
DOI
10.1016/j.carbpol.2018.10.121
PII: S0144-8617(18)31285-2
Knihovny.cz E-resources
- Keywords
- Click chemistry – oxime ligation, Dendritic cells, Drug delivery, Mannan, Mannosylated liposomes, Microfluidic mixing,
- MeSH
- Adjuvants, Immunologic pharmacology MeSH
- Antigens, Surface metabolism MeSH
- Candida glabrata chemistry MeSH
- Dendritic Cells immunology MeSH
- Hydroxylamines chemical synthesis chemistry MeSH
- Lectins, C-Type immunology MeSH
- Mannose-Binding Lectins immunology MeSH
- Humans MeSH
- Lipids chemical synthesis chemistry MeSH
- Liposomes chemistry immunology pharmacology MeSH
- Mannans chemistry immunology pharmacology MeSH
- Microfluidics methods MeSH
- Mice, Inbred BALB C MeSH
- Nanoparticles chemistry MeSH
- Mannose Receptor MeSH
- Receptors, Cell Surface immunology MeSH
- Click Chemistry MeSH
- Particle Size MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adjuvants, Immunologic MeSH
- Antigens, Surface MeSH
- Hydroxylamines MeSH
- Lectins, C-Type MeSH
- Mannose-Binding Lectins MeSH
- Lipids MeSH
- Liposomes MeSH
- Mannans MeSH
- Mannose Receptor MeSH
- Receptors, Cell Surface MeSH
New synthetic aminooxy lipid was designed and synthesized as a building block for the formulation of functionalised nanoliposomes (presenting onto the outer surface of aminooxy groups) by microfluidic mixing. Orthogonal binding of cellular mannan (Candida glabrata (CCY 26-20-1) onto the outer surface of functionalised nanoliposomes was modified by orthogonal binding of reducing termini of mannans to oxime lipids via a click chemistry reaction based on aminooxy coupling (oxime ligation). The aminooxy lipid was proved as a suitable active component for preparation of functionalised nanoliposomes by the microfluidic mixing method performed with the instrument NanoAssemblr™. This "on-chip technology" can be easily scaled-up. The structure of mannan-liposomes was visualized by transmission and scanning electron microscopy, including immunogold staining of recombinant mannan receptor bound onto mannosylated-liposomes. The observed structures are in a good correlation with data obtained by DLS, NTA, and TPRS methods. In vitro experiments on human and mouse dendritic cells demonstrate selective internalisation of fluorochrome-labelled mannan-liposomes and their ability to stimulate DC comparable to lipopolysaccharide. We describe a potentially new drug delivery platform for mannan receptor-targeted antimicrobial drugs as well as for immunotherapeutics. Furthermore, the platform based on mannans bound orthogonally onto the surface of nanoliposomes represents a self-adjuvanted carrier for construction of liposome-based recombinant vaccines for both systemic and mucosal routes of administration.
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