cDC1 Subtype-Specific In Vivo Targeting of Liposomes

Targeted modulation of immune cells holds great promise for improving therapeutic efficacy and minimizing systemic side effects; however, current strategies with nanocarriers often rely on untargeted or labor-intensive approaches. To bridge this gap, combining clinically approved nanocarrier systems like liposomes with highly specific targeting ligands provides a promising approach that could reach clinical application faster than other carriers. However, while studies have shown the potential of ligand-functionalized liposomes, most either lack sufficient immune cell subtype specificity or fail to translate their success from in vitro studies to the more complex environment in vivo. Therefore, a targeting approach was developed, based on a broad understanding of the colloidal system and functionalization procedure through an iterative process of physicochemical characterization and in vitro cell uptake studies. Liposomes were site-specifically functionalized with varying ratios of anti-CD11c or anti-CLEC9A antibodies, targeting receptors on conventional type 1 dendritic cells (cDC1). After identification of favorable particle parameters in vitro, optimized constructs were tested in in vivo targeting experiments. Flow cytometry revealed significantly enhanced uptake of anti-CD11c antibody-functionalized liposomes into various dendritic cell subtypes, while anti-CLEC9A antibody-functionalized liposomes showed significantly enhanced uptake only in cDC1 cells. In conclusion, a liposome-based cDC1 subtype-specific nanocarrier was developed and applied in vivo.