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Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood—brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the dist...

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Autores principales: Gao, Caifang, Liang, Jianming, Zhu, Ying, Ling, Chengli, Cheng, Zhekang, Li, Ruixiang, Qin, Jing, Lu, Weigen, Wang, Jianxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663921/
https://www.ncbi.nlm.nih.gov/pubmed/31384543
http://dx.doi.org/10.1016/j.apsb.2019.01.006
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author Gao, Caifang
Liang, Jianming
Zhu, Ying
Ling, Chengli
Cheng, Zhekang
Li, Ruixiang
Qin, Jing
Lu, Weigen
Wang, Jianxin
author_facet Gao, Caifang
Liang, Jianming
Zhu, Ying
Ling, Chengli
Cheng, Zhekang
Li, Ruixiang
Qin, Jing
Lu, Weigen
Wang, Jianxin
author_sort Gao, Caifang
collection PubMed
description Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood—brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.
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spelling pubmed-66639212019-08-05 Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy Gao, Caifang Liang, Jianming Zhu, Ying Ling, Chengli Cheng, Zhekang Li, Ruixiang Qin, Jing Lu, Weigen Wang, Jianxin Acta Pharm Sin B Original article Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood—brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy. Elsevier 2019-07 2019-01-11 /pmc/articles/PMC6663921/ /pubmed/31384543 http://dx.doi.org/10.1016/j.apsb.2019.01.006 Text en © 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Gao, Caifang
Liang, Jianming
Zhu, Ying
Ling, Chengli
Cheng, Zhekang
Li, Ruixiang
Qin, Jing
Lu, Weigen
Wang, Jianxin
Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title_full Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title_fullStr Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title_full_unstemmed Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title_short Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
title_sort menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663921/
https://www.ncbi.nlm.nih.gov/pubmed/31384543
http://dx.doi.org/10.1016/j.apsb.2019.01.006
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