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.

Autor: Bartheldyová E; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Turánek Knotigová P; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Zachová K; Department of Immunology and Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hněvotínská 3, 775 15 Olomouc, Czech Republic., Mašek J; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Kulich P; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Effenberg R; Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166, 28 Prague 6, Czech Republic., Zyka D; APIGENEX s.r.o., Poděbradská 173/5, Prague 9, 190 00, Czech Republic., Hubatka F; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Kotouček J; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Čelechovská H; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Héžová R; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Tomečková A; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Mašková E; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Fojtíková M; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic., Macaulay S; Malvern Instruments, Great Malvern, UK., Bystrický P; Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Malá Hora 10701/4A, 036 01 Martin, Slovakia., Paulovičová L; Department of Immunochemistry of Glycoconjugates, Immunology & Cell Culture Laboratory, Institute of Chemistry, Center for Glycomics Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia., Paulovičová E; Department of Immunochemistry of Glycoconjugates, Immunology & Cell Culture Laboratory, Institute of Chemistry, Center for Glycomics Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia. Electronic address: ema.paulovicova@savba.sk., Drož L; APIGENEX s.r.o., Poděbradská 173/5, Prague 9, 190 00, Czech Republic., Ledvina M; Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166, 28 Prague 6, Czech Republic. Electronic address: miroslav.ledvina@vscht.cz., Raška M; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic; Department of Immunology and Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hněvotínská 3, 775 15 Olomouc, Czech Republic. Electronic address: raskamil@uab.edu., Turánek J; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, v.v.i., Hudcova 70, 621 00 Brno, Czech Republic. Electronic address: turanek@vri.cz.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2019 Mar 01; Vol. 207, pp. 521-532. Date of Electronic Publication: 2018 Nov 29.
DOI: 10.1016/j.carbpol.2018.10.121
Abstrakt: 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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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