title: DC-SIGN-specific liposomal targeting and selective intracellular compound delivery to human myeloid dendritic cells: implications for HIV disease.
abstract: Myeloid dendritic cells (MyDCs), prime stimulators of antigen-specific immunity, can serve as one of the major reservoirs for human immunodeficiency virus type-1 (HIV-1). Utilizing mature monocyte-derived MyDCs generated with granulocyte/macrophage colony-stimulating factor, interleukin-4, and tumour necrosis factor-alpha as an in vitro model, we here present the first proof of concept for liposomal compound delivery to these cells by specifically addressing CD209, i.e. DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), a MyDC-associated C-type lectin implicated in the transmission of HIV-1 to T helper cells. By employing a liposomally entrapped tracer, calcein, we demonstrate by flow cytometry and mathematics a superior targeting efficacy for DC-SIGN, as compared with select other MyDC markers (CD1a, CD4, CD45R0, and CD83). Fluorescence microscopy reveals time-dependent surface binding and intracellular uptake of DC-SIGN-specific liposomes by both immature and mature MyDCs. This pilot study implies that liposomal targeting to CD209 and related C-type lectins may afford therapeutic intracellular drug delivery to MyDCs and other reservoir and nonreservoir cells susceptible to infection with HIV-1.
authors.affiliation: Laboratories of Immunology and Molecular Biology, LTBH Medical Research Institute, Robertson Building, Beverly Hills, CA 90211, USA. RGieseler@LTBH.org
authors.forename: R K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: G
authors.initials: G
authors.lastname: Marquitan
authors.forename: M J
authors.initials: MJ
authors.lastname: Hahn
authors.forename: L A
authors.initials: LA
authors.lastname: Perdon
authors.forename: W H P
authors.initials: WH
authors.lastname: Driessen
authors.forename: S M
authors.initials: SM
authors.lastname: Sullivan
authors.forename: M J
authors.initials: MJ
authors.lastname: Scolaro
mesh_terms: D015815:Cell Adhesion Molecules / Q000008:administration & dosage*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005452:Fluoresceins; D015658:HIV Infections / Q000628:therapy; D006801:Humans; D037181:Lectins, C-Type / Q000008:administration & dosage*; D008081:Liposomes; D008856:Microscopy, Fluorescence; D022423:Myeloid Cells / Q000166:cytology; D010865:Pilot Projects; D011956:Receptors, Cell Surface / Q000008:administration & dosage*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D005452:Fluoresceins; D037181:Lectins, C-Type; D008081:Liposomes; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C007740:fluorexon