For achievement of cancer immunotherapy, the induction of cytotoxic T lymphocyte (CTL)-based cellular immunity is required because CTL can kill tumor cells directly. Antigen presenting cell (APC)-specific antigen delivery and control of intracellular fate of antigen are important for induction of antigen-specific immune responses. Especially, antigen delivery to early endosomes or cytosol leads the induction of cellular immunity, which is called as “cross-presentation”. We previously reported intracellular delivery using liposomes modified with carboxylated polyglycidols or carboxylated dextrans to transfer antigen to inside of cells by pH-responsive fusion or destabilization of endosome (Biomaterials 2014, 35, 3091). The use of polysaccharide as backbone of pH-sensitive polymer has beneficial because of its biodegradability and biofunctions. In this study, hyaluronic acid (HA) derivative was designed as a multifunctional polymer having both pH-sensitivity and specificity to cells expressing CD44, which is known as a surface marker for various kinds of cells. Dendritic cell, the professional APC, also expresses CD44 on its surface and reportedly CD44-HA interaction induces activation of dendritic cell (Int J Cell Bio, 2015, 563818). Here, synthesis of HA derivatives, activation of dendritic cells by HA derivatives, preparation of HA derivative-modified liposomes and their antigen delivery performance to dendritic cells were examined. Results show the importance of HA backbone and side chain structures on their intracellular delivery performance and activation of dendritic cells.

Development of hyaluronic acid derivative-modified liposomes as dendritic cell-specific antigen delivery carriers

255th National Meeting (2018)

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