Targeting of Immune Cells with Trimannosylated Liposomes

Dendritic cells (DCs) are a compelling target in cancer immunotherapy as they initialize strong antigen‐specific immune responses. Drug delivery systems (DDSs) such as liposomes provide the opportunity to deliver antigens and immunostimulatory molecules to DCs, which in turn initiate an antigen‐specific immune response. To address predominantly DCs, DDSs need to be equipped with targeting moieties. This study evaluates liposomes, bearing the oligosaccharide trimannose on their surface, for their ability to address DCs in vitro and in vivo. Trimannose as a saccharidic structure is known to be recognized by receptors on the surface of DCs. To obtain trimannosylated liposomes, azide‐bearing trimannose is coupled to alkyne‐functionalized hyperbranched polyglycerol ( hb PG) with a bis(hexadecyl)glycerol (BisHD) anchor in a Cu(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC). To enable tracking of the liposomes in vivo, the trimannosylated BisHD‐ hb PG lipids are radiolabeled with 18 F in a CuAAC. Subsequently, liposomes are produced via the thin‐film hydration method followed by extrusion. The behavior of the trimannosylated liposomes is evaluated in in vitro cell binding assays and in vivo µPET and ex vivo biodistribution studies in healthy C57BL/6 mice and the results are compared to similar liposomes not bearing trimannose on their surface.