Nikpoor Amin Reza, Tavakkol-Afshari Jalil, Gholizadeh Zahra, Sadri Kayvan, Babaei Mohammad Hossein, Chamani Jamshidkhan, Badiee Ali, Jalali Seyed Amir, Jaafari Mahmoud Reza
Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad 919677-3117, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad 913881-3944, Iran.
Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad 919677-3117, Iran.
Int J Pharm. 2015 Nov 10;495(1):162-170. doi: 10.1016/j.ijpharm.2015.08.048. Epub 2015 Aug 21.
Monoclonal antibodies are routinely used as tools in immunotherapies against solid tumors. However, administration of monoclonal antibodies may cause undesired side effects due to their accumulation in non-targeted organs. Nanoliposomes of less than 200 nm can target antibodies to tumors by enhanced permeation and retention (EPR) mechanisms. To direct monoclonal antibodies to tumors, nanoliposomes encapsulating intravenous immunoglobulin (IVIG) as a model antibody were prepared. The liposomes had average diameters of 100 nm and encapsulation efficiencies of 31 to 46%. They showed less than 10% release in plasma at 37°C up to seven days. The secondary and tertiary structures of liposome-encapsulated antibodies were analyzed by circular dichroism (CD) spectroscopy. The near and far-UV spectra analyses revealed no obvious conformational changes in the structures of the encapsulated antibodies. The biodistribution of free and liposome-encapsulated iodinated antibodies was investigated in mice bearing C-26 colon carcinoma tumors. The accumulation of liposome-encapsulated antibodies in tumors was significantly greater than that of free antibodies due to the EPR effect. The PEGylated liposomes were more efficient in the delivery of antibodies to the tumor site than non-PEGylated liposomes. We conclude that administration of monoclonal antibodies in PEGylated liposomes is more efficient than administration of non-encapsulated monoclonal antibodies for solid tumor immunotherapy.
单克隆抗体通常用作针对实体瘤的免疫治疗工具。然而,由于单克隆抗体在非靶向器官中的积累,其给药可能会导致不良副作用。小于200 nm的纳米脂质体可通过增强渗透与滞留(EPR)机制将抗体靶向肿瘤。为了将单克隆抗体导向肿瘤,制备了包裹静脉注射免疫球蛋白(IVIG)作为模型抗体的纳米脂质体。这些脂质体的平均直径为100 nm,包封率为31%至46%。在37°C下,它们在血浆中的释放率在长达七天的时间内低于10%。通过圆二色性(CD)光谱分析脂质体包裹抗体的二级和三级结构。近紫外和远紫外光谱分析表明,包裹抗体的结构没有明显的构象变化。在携带C-26结肠癌肿瘤的小鼠中研究了游离和脂质体包裹的碘化抗体的生物分布。由于EPR效应,脂质体包裹抗体在肿瘤中的积累明显高于游离抗体。聚乙二醇化脂质体在将抗体递送至肿瘤部位方面比非聚乙二醇化脂质体更有效。我们得出结论,对于实体瘤免疫治疗,聚乙二醇化脂质体中给药单克隆抗体比未包裹的单克隆抗体给药更有效。