DC‐SIGN‐Specific Liposomal Targeting and Selective Intracellular Compound Delivery to Human Myeloid Dendritic Cells: Implications for HIV Disease

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‐α 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.