Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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
_version_ 1783310710083682304
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
work_keys_str_mv AT mahmudhafizah targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT kasaitomonari targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT khayraniaprilianacahya targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT asakuramami targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT ooaungkoko targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT dujuan targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT vaidyanatharun targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT elghlbansamah targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT mizutaniakifumi targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT senoakimasa targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT murakamihiroshi targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT masudajunko targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein
AT senomasaharu targetingglioblastomacellsexpressingcd44withliposomesencapsulatingdoxorubicinanddisplayingchlorotoxiniggfcfusionprotein