Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Biomaterials. 2017 Oct;141:272-283. doi: 10.1016/j.biomaterials.2017.07.001. Epub 2017 Jul 3.
Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects. In this study, CpG-DNA, a ligand to Toll-like receptor 9 (TLR9) expressing in endosomes of DCs, was introduced to MGlu-HPG-modified liposomes containing cationic lipids using two complexation methods (Pre-mix and Post-mix) for additional activation of antigen-specific immunity. For Pre-mix, thin membrane of lipids and polymers were dispersed by a mixture of antigen/CpG-DNA. For Post-mix, CpG-DNA was added to pre-formed liposomes. Both Pre-mix and Post-mix delivered CpG-DNA to DC endosomes, where TLR9 is expressing, more efficiently than free CpG-DNA solution did. These liposomes promoted cytokine production from DCs and the expression of co-stimulatory molecules in vitro and induced antigen-specific immune responses in vivo. Both Pre-mix and Post-mix exhibited strong antitumor effects compared with conventional pH-sensitive polymer-modified liposomes. Results show that inclusion of multiple adjuvant molecules into pH-sensitive polymer-modified liposomes and suitable CpG-DNA complexation methods are important to design potent vaccine carriers.
用于癌症免疫治疗的高效疫苗载体需要两个功能:向树突状细胞 (DC) 递呈抗原和激活 DC,即所谓的佐剂效应。我们之前报道了使用 pH 敏感聚合物(如 3-甲基戊二酰化超支化聚(缩水甘油)(MGlu-HPG))修饰的脂质体作为抗原递呈系统,用于诱导抗原特异性免疫反应。我们报道过,向 MGlu-HPG 修饰的脂质体中加入阳离子脂质可以激活 DC 并增强抗肿瘤作用。在这项研究中,CpG-DNA(一种在 DC 内体中表达的 Toll 样受体 9(TLR9)的配体)通过两种复合方法(预混合和后混合)被引入到含有阳离子脂质的 MGlu-HPG 修饰的脂质体中,以进一步激活抗原特异性免疫。对于预混合,将抗原/CpG-DNA 的混合物分散在薄的脂质和聚合物膜中。对于后混合,将 CpG-DNA 添加到预先形成的脂质体中。与游离 CpG-DNA 溶液相比,这两种方法都能更有效地将 CpG-DNA 递送到 DC 内体,TLR9 就在内体中表达。这些脂质体在体外促进了 DC 细胞因子的产生和共刺激分子的表达,并在体内诱导了抗原特异性免疫反应。与传统的 pH 敏感聚合物修饰的脂质体相比,预混合和后混合都表现出强烈的抗肿瘤作用。结果表明,将多种佐剂分子纳入 pH 敏感聚合物修饰的脂质体中和适当的 CpG-DNA 复合方法对于设计有效的疫苗载体非常重要。
Biomaterials. 2013-4-29
Biomaterials. 2014-1-6
J Hematol Oncol. 2024-4-2
Bioact Mater. 2024-3-10
Int J Mol Sci. 2023-1-19
Front Immunol. 2022
Pharmaceutics. 2022-7-11