Department of Applied Chemistry, Osaka Prefecture University, Gakuen-cho, Naka-ku, Sakai, Japan.
Biomaterials. 2010 Feb;31(5):943-51. doi: 10.1016/j.biomaterials.2009.10.006. Epub 2009 Oct 21.
By modification of liposomes with poly(glycidol) derivatives such as succinylated poly(glycidol) and 3-methylglutarylated poly(glycidol), we have developed functional liposomes that generate fusion ability at mildly acidic pH. We investigated the feasibility of these polymer-modified liposomes as a carrier of antigenic proteins for induction of cellular immunity. These pH-sensitive fusogenic liposomes encapsulating ovalbumin (OVA) were applied to DC2.4 cells, a murine dendritic cell line. Observation with confocal laser scanning microscopy showed that these polymer-modified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion with endosomal membranes. Murine bone marrow-derived dendritic cells treated with polymer-modified liposomes encapsulating OVA stimulated CD8-OVA1.3 cells more strongly than OT4H.1D5 cells, indicating that the liposomes induced MHC class I-restricted presentation. Furthermore, administration of the polymer-modified, OVA-loaded liposomes from nasal cavities of mice induced stronger cellular immune responses than the OVA-loaded plain liposomes. Because the ability of the polymer-modified liposomes to activate cellular immunity was comparable to that of Freund's complete adjuvant, which is a widely used adjuvant, they potentially have use in production of efficient vaccines for immunotherapy.
通过对脂质体进行聚（缩水甘油）衍生物（如琥珀酰化聚（缩水甘油）和 3-甲基戊二酰化聚（缩水甘油））的修饰，我们开发了在酸性 pH 值下具有融合能力的功能性脂质体。我们研究了这些聚合物修饰的脂质体作为抗原蛋白载体诱导细胞免疫的可行性。这些 pH 敏感的融合脂质体包封卵清蛋白（OVA）后应用于 DC2.4 细胞，一种鼠树突状细胞系。共聚焦激光扫描显微镜观察显示，这些聚合物修饰的脂质体被细胞有效摄取，随后将其内容物递送到细胞质中，可能通过与内体膜融合。用包封 OVA 的聚合物修饰的脂质体处理的鼠骨髓来源的树突状细胞比 OT4H.1D5 细胞更强烈地刺激 CD8-OVA1.3 细胞，表明脂质体诱导 MHC Ⅰ类限制的呈递。此外，从鼻腔给予聚合物修饰的、OVA 负载的脂质体比 OVA 负载的普通脂质体引起更强的细胞免疫反应。由于聚合物修饰的脂质体激活细胞免疫的能力与广泛使用的弗氏完全佐剂相当，因此它们有可能用于生产有效的免疫治疗疫苗。
