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Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein
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, OC...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877520/ https://www.ncbi.nlm.nih.gov/pubmed/29495404 http://dx.doi.org/10.3390/ijms19030659 |
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author | 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 |
author_facet | 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 |
author_sort | Mahmud, Hafizah |
collection | PubMed |
description | 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-5877520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58775202018-04-09 Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein 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 Int J Mol Sci Article 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 IC(50) 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. MDPI 2018-02-26 /pmc/articles/PMC5877520/ /pubmed/29495404 http://dx.doi.org/10.3390/ijms19030659 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title | Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title_full | Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title_fullStr | Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title_full_unstemmed | Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title_short | Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein |
title_sort | targeting glioblastoma cells expressing cd44 with liposomes encapsulating doxorubicin and displaying chlorotoxin-igg fc fusion protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877520/ https://www.ncbi.nlm.nih.gov/pubmed/29495404 http://dx.doi.org/10.3390/ijms19030659 |
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