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Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

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
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(3), 659;
Received: 27 December 2017 / Revised: 13 February 2018 / Accepted: 23 February 2018 / Published: 26 February 2018
(This article belongs to the Special Issue Nanotechnology in Cancer Treatment)
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, 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
Keywords: M-CTX-Fc; liposome; glioblastoma cells; specific targeting; doxorubicin; MMP-2 M-CTX-Fc; liposome; glioblastoma cells; specific targeting; doxorubicin; MMP-2
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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.

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