Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model.
As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanolip...
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doaj-52269d041b5d4604830e8db4f95d1f602020-11-25T00:12:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10373610.1371/journal.pone.0103736Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model.Jia LinSarah ShigdarDing Zhi FangDognxi XiangMing Q WeiAndrew DanksLingxue KongLianghong LiLiang QiaoWei DuanAs a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.http://europepmc.org/articles/PMC4114873?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jia Lin Sarah Shigdar Ding Zhi Fang Dognxi Xiang Ming Q Wei Andrew Danks Lingxue Kong Lianghong Li Liang Qiao Wei Duan |
spellingShingle |
Jia Lin Sarah Shigdar Ding Zhi Fang Dognxi Xiang Ming Q Wei Andrew Danks Lingxue Kong Lianghong Li Liang Qiao Wei Duan Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. PLoS ONE |
author_facet |
Jia Lin Sarah Shigdar Ding Zhi Fang Dognxi Xiang Ming Q Wei Andrew Danks Lingxue Kong Lianghong Li Liang Qiao Wei Duan |
author_sort |
Jia Lin |
title |
Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
title_short |
Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
title_full |
Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
title_fullStr |
Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
title_full_unstemmed |
Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
title_sort |
improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment. |
url |
http://europepmc.org/articles/PMC4114873?pdf=render |
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