Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-0080, Japan.
Department of Chemistry, Biochemistry Division, Faculty of Science, El Menoufia University, Shebin El Kom, Menoufia 32511, Egypt.
Int J Mol Sci. 2018 Feb 26;19(3):659. doi: 10.3390/ijms19030659.
We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, , , and , this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100-150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics.
我们最近通过从 U251MG 细胞中富集依赖透明质酸的球体形成群体，成功建立了人胶质母细胞瘤细胞的异种移植模型，这些群体被命名为 U251MG-P1 细胞。由于 U251MG-P1 细胞已被证实表达 CD44 以及主要的干性标记基因、、、和，这个表达 CD44 的群体似乎主要由未分化细胞组成。评估对抗癌药物的敏感性时，我们发现 U251MG-P1 细胞对阿霉素敏感，IC 为 200 nM。尽管阿霉素有严重的副作用，但建立针对未分化胶质母细胞瘤细胞群体的有效治疗方法是必要的。我们之前设计了一种没有铰链序列的与人 IgG Fc 区域融合的氯毒素肽（M-CTX-Fc），它对胶质母细胞瘤细胞系 A172 的生长抑制作用比原始氯毒素肽更强。将这些结果结合在一起，我们设计了 M-CTX-Fc 缀合的脂质体，包载阿霉素，并将 U251MG-P1 细胞作为本研究的靶模型。用 M-CTX-Fc 修饰的脂质体设计成直径约为 100-150nm，并表现出高包封效率、足够的抗癌药物载药量、增强的体外细胞摄取的抗肿瘤效果；M-CTX-Fc-L-Dox 在抑制体内肿瘤生长方面具有很大的潜力，它可以作为靶向输送其他治疗剂的模板。
