Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein.
Hafizah MahmudTomonari KasaiAprilliana Cahya KhayraniMami AsakuraAung Ko Ko OoJuan DuArun VaidyanathSamah El-GhlbanAkifumi MizutaniAkimasa SenoHiroshi MurakamiJunko MasudaMasaharu SenoPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- drug delivery
- gene expression
- transcription factor
- endothelial cells
- bone marrow
- cell death
- small molecule
- photodynamic therapy
- high resolution
- machine learning
- emergency department
- multidrug resistant
- epithelial mesenchymal transition
- mass spectrometry
- klebsiella pneumoniae
- drug induced
- genome wide
- big data
- induced pluripotent stem cells
- adverse drug