論文

査読有り 国際誌
2018年2月26日

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

International journal of molecular sciences
  • Hafizah Mahmud
  • ,
  • Tomonari Kasai
  • ,
  • Apriliana Cahya Khayrani
  • ,
  • Mami Asakura
  • ,
  • Aung Ko Ko Oo
  • ,
  • Juan Du
  • ,
  • Arun Vaidyanath
  • ,
  • Samah El-Ghlban
  • ,
  • Akifumi Mizutani
  • ,
  • Akimasa Seno
  • ,
  • Hiroshi Murakami
  • ,
  • Junko Masuda
  • ,
  • Masaharu Seno

19
3
記述言語
英語
掲載種別
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, 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.

リンク情報
DOI
https://doi.org/10.3390/ijms19030659
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29495404
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877520
URL
http://www.mdpi.com/1422-0067/19/3/659
URL
http://orcid.org/0000-0002-9664-9490

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