Synthesis of defined oligohyaluronates-decorated liposomes and interaction with lung cancer cells. (15th November 2020)

• Record Type: Journal Article
• Authors: Cano, Maria Emilia; Lesur, David; Bincoletto, Valeria; Gazzano, Elena; Stella, Barbara; Riganti, Chiara; Arpicco, Silvia; Kovensky, José
• Is Part Of: Carbohydrate polymers. Volume 248(2020)
• Publication Date: 2020-11-15
• Subjects: Hyaluronic acid -- Oligosaccharides -- Liposomes -- HA-CD44 interaction; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2020.116798
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Three phospholipo-oligohyaluronates (HA-DP) were synthesized to prepare decorated liposomes. The uptake of these HA-DP-liposomes is higher in lung cancer cell lines with high CD44 expression. HA-DP-liposomes did not show cytotoxicity or inflammatory effects. Abstract: In this work hyaluronic acid (HA) oligosaccharides with degree of polymerization (DP) 4, 6 and 8, obtained by enzymatic depolymerization of HA, were conjugated to a PEG-phospholipid moiety. The products (HA-DP4, HA-DP6 and HA-DP8) were used to prepare decorated liposomes. The cellular uptake of HA-DP4, HA-DP6 and HA-DP8-decorated fluorescently labelled liposomes was significantly higher (12 to 14-fold) in lung cancer cell lines with high CD44 expression than in those with low CD44 expression, suggesting a receptor-mediated entry of HA-conjugated formulations. Competition assays showed that the uptake followed this rank order: HA-DP8>HA-DP6>HA-DP4 liposomes. Moreover, they are capable of a faster interaction with CD44, followed by phagocytosis, than HA liposomes obtained from HA of higher molecular weight (4800 and 14800 Da). HA-DP4, HA-DP6 and HA-DP8-liposomes did not show cytotoxicity or inflammatory effects. Overall, we propose our new HA-DP oligosaccharides as biocompatible and effective tools for a potential drug delivery to CD44-positive cells.