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

Carbohydr Polym. 2019 Mar 1;207:521-532. doi: 10.1016/j.carbpol.2018.10.121. Epub 2018 Nov 29.


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.

Keywords: Click chemistry – oxime ligation; Dendritic cells; Drug delivery; Mannan; Mannosylated liposomes; Microfluidic mixing.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Surface / metabolism
  • Candida glabrata / chemistry
  • Click Chemistry
  • Dendritic Cells / immunology*
  • Humans
  • Hydroxylamines / chemical synthesis
  • Hydroxylamines / chemistry
  • Lectins, C-Type / immunology*
  • Lipids / chemical synthesis
  • Lipids / chemistry
  • Liposomes / chemistry
  • Liposomes / immunology*
  • Liposomes / pharmacology
  • Mannans / chemistry
  • Mannans / immunology*
  • Mannans / pharmacology
  • Mannose-Binding Lectins / immunology*
  • Mice, Inbred BALB C
  • Microfluidics / methods
  • Nanoparticles / chemistry*
  • Particle Size
  • Receptors, Cell Surface / immunology*


  • Adjuvants, Immunologic
  • Antigens, Surface
  • Hydroxylamines
  • Lectins, C-Type
  • Lipids
  • Liposomes
  • Mannans
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor