Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Biomaterials. 2010 May;31(14):4139-45. doi: 10.1016/j.biomaterials.2010.01.086. Epub 2010 Feb 10.
The diverse characteristics of immunoliposomes provide advantages for utilization in drug delivery systems. In this study, we fused the antibody affinity motif of protein A (ZZ) with Gaussia luciferase (GLase). The fused protein conjugated with an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (GLase-ZZ-His-mAb) was effectively delivered into glioma cells expressing an activated EGFR mutant (EGFRvIII) and the bioluminescence was visualized in the cells. Immunoliposomes were further constructed with DSPE-PEG-MAL for covalent GLase-ZZ-His-mAb conjugation. A fluorescence dye (HPTS) encapsulated in immunoliposomes conjugated with GLase-ZZ-His-mAb was effectively delivered into EGFRvIII-expressing glioma cells. In a murine xenograft model of glioma, moreover, specific targeting of the immunoliposomes was visualized in the tumor. This new bifunctional immunoliposome system has the potential for drug delivery and imaging in vivo.
免疫脂质体的多种特性为其在药物传递系统中的应用提供了优势。在本研究中，我们将蛋白 A 的抗体亲和结构域（ZZ）与海肾荧光素酶（GLase）融合。融合蛋白与抗表皮生长因子受体（EGFR）单克隆抗体（GLase-ZZ-His-mAb）缀合，可有效递送至表达激活型 EGFR 突变体（EGFRvIII）的神经胶质瘤细胞，并且可以在细胞中可视化生物发光。然后，用 DSPE-PEG-MAL 进一步构建免疫脂质体以实现 GLase-ZZ-His-mAb 的共价缀合。与 GLase-ZZ-His-mAb 缀合的免疫脂质体包封的荧光染料（HPTS）可有效递送至表达 EGFRvIII 的神经胶质瘤细胞。此外，在神经胶质瘤的小鼠异种移植模型中，可在肿瘤中观察到免疫脂质体的特异性靶向。这种新的双功能免疫脂质体系统具有体内药物传递和成像的潜力。
