Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5726-31. doi: 10.1016/j.bmcl.2010.08.011. Epub 2010 Aug 6.
A novel HER2-targeted carrier was developed using bionanocapsules (BNCs). Bionanocapsules (BNCs) are 100-nm hollow nanoparticles composed of the L-protein of hepatitis B virus surface antigen. An affibody of HER2 was genetically displayed on the BNC surface (Z(HER2)-BNC). For the investigation of binding affinity, Z(HER2)-BNC was incubated with the cancer cell lines SK-BR-3 (HER2 positive), and MDA-MB-231 (HER2 negative). For analysis of HER2 targeting specificity, Z(HER2)-BNC or Z(WT)-BNC (without affibody) was incubated with both SK-BR-3 and MDA-MB-231 cells by time lapse and concentration. For the delivery of encapsulated molecules (calcein), fluorescence of Z(HER2)-BNC mixed with liposomes was also compared with that of Z(WT)-BNC and nude liposomes by incubation with SK-BR-3 cells. As a result, Z(HER2)-BNC-liposome complex demonstrated the delivery to HER2-expressing cells (SK-BR-3) with a high degree of specificity. This indicates that genetically engineered BNCs are promising carrier for cancer treatment.
一种新型的 HER2 靶向载体是使用生物纳米胶囊(BNC)开发的。生物纳米胶囊(BNC)是由乙肝病毒表面抗原 L 蛋白组成的 100nm 空心纳米颗粒。HER2 的亲和体在 BNC 表面进行基因展示(Z(HER2)-BNC)。为了研究结合亲和力,将 Z(HER2)-BNC 与 SK-BR-3(HER2 阳性)和 MDA-MB-231(HER2 阴性)癌细胞系孵育。为了分析 HER2 靶向特异性,通过时间推移和浓度将 Z(HER2)-BNC 或 Z(WT)-BNC(无亲和体)与 SK-BR-3 和 MDA-MB-231 细胞孵育。对于封装分子(钙黄绿素)的递送,通过与 SK-BR-3 细胞孵育,比较 Z(HER2)-BNC 与脂质体混合的荧光与 Z(WT)-BNC 和裸脂质体的荧光。结果,Z(HER2)-BNC-脂质体复合物表现出对 HER2 表达细胞(SK-BR-3)的高度特异性递送。这表明基因工程 BNC 是一种有前途的癌症治疗载体。