CD44, the main receptor of hyaluronic acid (HA), is overexpressed in several pathological conditions and therefore can be seen as an interesting target for therapeutic intervention. Here, an approach using HA-coated chitosan (CS)-triphosphate (TPP) nanoparticles is investigated, using CS with different molecular weight (25 and 684 kDa), which influences HA presentation, and enzymatic and pH stability. In a study of nuclease stability, post-digestion of nanoparticles with chitosanase reveals that pDNA is at least partially degraded by DNAse; this may suggest that literature results overestimate the polyplex stability against nucleases. Using cells with a significantly different CD44 expression (RAW 264.7 macrophages-high levels; K562 leukemia cells-low levels; Kelly neuroblastoma cells-absent), the selectivity of CD44-mediated transfection is proven. Further, using luciferase pDNA and then later anti-luc siRNA, low MW CS-based nanoparticles show the best results despite a lower internalization efficiency; this effect is ascribed to a more efficient endosomal disruption and nucleic acid de-complexation.
Keywords: CD44; hyaluronic acid; macrophages; nanoparticles; receptor-mediated internalization.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.