title: Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.
abstract: Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease. Cationic lipid inclusion improved their pH sensitivity at weakly acidic pH and association of liposomes with murine dendritic cell (DC) lines. Cationic lipid-incorporated liposomes delivered entrapped ovalbumin (OVA) molecules not only to cytosol but also to endosome/lysosome. Treatment with cationic lipid-incorporated liposomes induced up-regulation of antigen presentation-involved molecules on DCs, the promotion of cytokine production, and antigen presentation via both major histocompatibility complex (MHC) class I and II molecules. Especially, antigen presentation via MHC class II was promoted by cationic lipid inclusion, which might correspond to efficient endosome/lysosome delivery of OVA. Subcutaneous administration of OVA-loaded cationic lipid-incorporated liposomes induced antigen-specific antibody production in serum and Th1-dominant immune responses in the spleen. Furthermore, administration of the cationic lipid-incorporated liposomes to mice bearing E.G7-OVA tumor more significantly reduced the tumor volume than liposomes without cationic lipids. Therefore, cationic lipid inclusion into pH-sensitive polymer-modified liposomes, which can achieve both efficient antigen intracellular delivery and activation of antigen presenting cell, is an effective approach to develop antigen carriers for efficient cancer immunotherapy.
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Yuta
authors: Y
authors: Yoshizaki
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Eiji
authors: E
authors: Yuba
authors: Terumo Corp., Ltd., Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Naoki
authors: N
authors: Sakaguchi
authors: Terumo Corp., Ltd., Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Kazunori
authors: K
authors: Koiwai
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Atsushi
authors: A
authors: Harada
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: kono@chem.osakafu-u.ac.jp.
authors: Kenji
authors: K
authors: Kono
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry*; D002412:Cations; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005977:Glutarates / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007167:Immunotherapy / Q000379:methods*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D010713:Phosphatidylcholines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*
chemical_list: D000941:Antigens; D002412:Cations; D005977:Glutarates; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D011108:Polymers; D011409:Propylene Glycols
keywords: Adjuvant; Cancer immunotherapy; Cationic lipid; Cellular immunity; Dendritic cell; pH-sensitive liposome