Journal
BIOMATERIALS
Volume 120, Issue -, Pages 32-45Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.12.021
Keywords
pH-sensitive liposome; Curdlan; beta-glucan; Mannan; Cancer immunotherapy; Dendritic cell
Funding
- Ministry of Education, Science, Sports, and Culture in Japan [15H03024, 25750177]
- Grants-in-Aid for Scientific Research [15H03024, 25750177, 15J12180] Funding Source: KAKEN
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For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability. For this study, bioactive polysaccharide-based pH-sensitive polymers were constructed to achieve not only cytoplasmic delivery of antigen but also activation of DCs. Curdlan and mannan were used as bioactive polysaccharides because they are known to activate DCs via their respective interactions with Dectin-1 and Dectin-2. Carboxylated curdlan and mannan promoted Th1 cytokine production from DCs, indicating the activation of DCs by these polysaccharide derivatives. These polymer-modified liposomes released their contents at weakly acidic pH and delivered model antigenic proteins into cytosol of DCs. Subcutaneous administration of curdlan derivative-modified or mannan derivative-modified liposomes induced strong antigen-specific immune responses and stronger antitumor effects than those of liposomes modified with dextran derivative. Therefore, bioactive polysaccharide-modified liposomes that achieve both cytoplasmic delivery of antigen and activation of DCs are promising for cancer immunotherapy. (C) 2016 Elsevier Ltd. All rights reserved.
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