3 2 2 Antibodies Immunoliposomes are liposomes coupled with anti

3.2.2. Antibodies Immunowww.selleckchem.com/products/Rapamycin.html liposomes are liposomes coupled with antibodies which can be used to target cell-specific antigens. In the case of phagocyte targeting, the use of nonspecific and monoclonal antibodies can lead to liposome opsonisation and uptake by macrophages. In vivo liposomes interact with a wide variety of serum proteins including immunoglobulins, Inhibitors,research,lifescience,medical apolipoproteins, and complement proteins [42, 53] and may also activate complement leading to enhanced uptake by the MPS. However, protein interaction, complement activation, and opsonisation depend greatly on the physicochemical properties of the liposomes such as size, surface charge, cholesterol content, and

lipid composition [42, 53]. For example, some studies Inhibitors,research,lifescience,medical have reported complement activation to be greater with increasing liposome size [53] although observed activation has not always been of significance [24]. Immunoglobulins (Igs) are recognised by Fc receptors on the surface of phagocytic cells which are involved in phagocytosis as well as antigen presentation [21] (Figure 1). Interest has focused on the Inhibitors,research,lifescience,medical FcγRI receptor as a target which recognises IgG and is expressed by monocytes, macrophages,

activated neutrophils, and DCs [21]. Opsonisation is generally Fc-receptor mediated and has previously been shown to significantly enhance liposome uptake by monocytes and macrophages [32]. Opsonisation of non-immunoliposomes by immunoglobulins, Inhibitors,research,lifescience,medical for example, IgM and IgG, can also occur in vivo leading to enhanced uptake by macrophages [53]. Antibodies have been coupled to the surface of liposomes or distally via their Fc-region to liposome-attached PEG [31, 32]. Koning et al. showed increased Inhibitors,research,lifescience,medical Kupffer cell uptake with greater antibody surface density [31, 32]. Dendritic cells have been targeted with histidine-tagged antibody fragments attached to a novel chelator lipid, 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA), incorporated into stealth liposomes via the DC receptors DEC-205 and CD11c [21]. 3.2.3.

Lectins Immune cells including alveolar macrophages, peritoneal macrophages, monocyte-derived dendritic cells, and Kupffer cells constitutively express high levels of the mannose receptor (MR). Macrophages and DCs can therefore be targeted via mannosylated nanoparticles (Figure 1). The MR is a C-type lectin 175-kD type I transmembrane protein [62, 63] whose ligands possess a terminal Batimastat nonreducing sugar such as mannose, glucose, N-acetylglucosamine, and fucose [64, 65]. These receptors play numerous roles in immune function including antigenic recognition, endocytosis, and antigen presentation, and are critically involved in homeostatic maintenance, inflammation and immune responses [66, 67]. Hence MR can identify and engulf pathogens such as Mycobacterium tuberculosis and Leishmania obviously donovani via surface sugar antigens.

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