Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein
AbstractWe 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, OCT3/4, SOX2, KLF4 and Nanog, 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 IC50 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. View Full-Text
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Mahmud, H.; Kasai, T.; Khayrani, A.C.; Asakura, M.; Oo, A.K.K.; Du, J.; Vaidyanath, A.; El-Ghlban, S.; Mizutani, A.; Seno, A.; Murakami, H.; Masuda, J.; Seno, M. Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. Int. J. Mol. Sci. 2018, 19, 659.
Mahmud H, Kasai T, Khayrani AC, Asakura M, Oo AKK, Du J, Vaidyanath A, El-Ghlban S, Mizutani A, Seno A, Murakami H, Masuda J, Seno M. Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. International Journal of Molecular Sciences. 2018; 19(3):659.Chicago/Turabian Style
Mahmud, Hafizah; Kasai, Tomonari; Khayrani, Apriliana Cahya; Asakura, Mami; Oo, Aung Ko Ko; Du, Juan; Vaidyanath, Arun; El-Ghlban, Samah; Mizutani, Akifumi; Seno, Akimasa; Murakami, Hiroshi; Masuda, Junko; Seno, Masaharu. 2018. "Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein." Int. J. Mol. Sci. 19, no. 3: 659.
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