Anti-CD44-Conjugated Olive Oil Liquid Nanocapsules for Targeting Pancreatic Cancer Stem Cells

The latest trends in cancer research and nanomedicine focus on using nanocarriers to target cancer stem cells (CSCs). Specifically, lipid liquid nanocapsules are usually developed as nanocarriers for lipophilic drug delivery. Here, we developed olive oil liquid NCs ((OLNCs)-L-2) functionalized by covalent coupling of an anti-CD44-fluorescein isothiocyanate antibody (alpha CD44). First, (OLNCs)-L-2 are formed by a core of olive oil surrounded by a shell containing phospholipids, a nonionic surfactant, and deoxycholic acid molecules. Then, (OLNCs)-L-2 were coated with an aCD44 antibody (alpha CD44-(OLNC)-L-2). The optimization of an alpha CD44 coating procedure, a complete physicochemical characterization, as well as clear evidence of their efficacy in vitro and in vivo were demonstrated. Our results indicate the high targeted uptake of these alpha CD44-(OLNCs)-L-2, and the increased antitumor efficacy (up to four times) of paclitaxel-loaded-alpha CD44-(OLNC)-L-2 compared to free paclitaxel in pancreatic CSCs (PCSCs). Also, alpha CD44-(OLNCs)-L-2 were able to selectively target PCSCs in an orthotopic xenotransplant in vivo model.