Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma
Yu-Ling Lin, 1,* Xiao-Fan Huang, 2, 3,* Kai-Fu Chang, 2, 3,* Kuang-Wen Liao, 4–6 Nu-Man Tsai 2, 7 1Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan, Republic of China; 2Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Tai...
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Dove Medical Press
2020
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oai:doaj.org-article:d70ca8a6260647eeaed52dae7e9da38e2021-12-02T10:51:13ZEncapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma1178-2013https://doaj.org/article/d70ca8a6260647eeaed52dae7e9da38e2020-01-01T00:00:00Zhttps://www.dovepress.com/encapsulated-n-butylidenephthalide-efficiently-crosses-the-bloodndashb-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yu-Ling Lin, 1,* Xiao-Fan Huang, 2, 3,* Kai-Fu Chang, 2, 3,* Kuang-Wen Liao, 4–6 Nu-Man Tsai 2, 7 1Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan, Republic of China; 2Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, Republic of China; 3Institute of Medicine of Chung Shun Medical University, Taichung 40201, Taiwan, Republic of China; 4Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan, Republic of China; 5Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30010, Taiwan, Republic of China; 6Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, Republic of China; 7Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Nu-Man TsaiDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, TaiwanTel +886-4-24730022 ext. 12411Fax +886-4-23248171Email numan@csmu.edu.twBackground: n-Butylidenephthalide (BP) has anti-tumor effects on glioblastoma. However, the limitation of BP for clinical application is its unstable structure. A polycationic liposomal polyethylenimine (PEI) and polyethylene glycol (PEG) complex (LPPC) has been developed to encapsulate BP for drug structure protection. The purpose of this study was to investigate the anti-cancer effects of the BP/LPPC complex on glioblastoma in vitro and in vivo.Methods: DBTRG-05MG tumor bearing xenograft mice were treated with BP and BP/LPPC and then their tumor sizes, survival, drug biodistribution were measured. RG2 tumor bearing F344 rats also treated with BP and BP/LPPC and then their tumor sizes by magnetic resonance imaging for evaluation blood–brain barrier (BBB) across and drug therapeutic effects. After treated with BP/LPPC in vitro, cell uptake, cell cycle and apoptotic regulators were analyzed for evaluation the therapeutic mechanism.Results: In athymic mice, BP/LPPC could efficiently suppress tumor growth and prolong survival. In F334 rats, BP/LPPC crossed the BBB and led to tumor shrinkage. BP/LPPC promoted cell cycle arrest at the G 0/G 1 phase and triggered the extrinsic and intrinsic cell apoptosis pathways resulting cell death. BP/LPPC also efficiently suppressed VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 expression.Conclusion: BP/LPPC was rapidly and efficiently transported to the tumor area across the BBB and induced cell apoptosis, anti-angiogenetic and anti-metastatic effects in vitro and in vivo.Keywords: glioblastoma, n-butylidenephthalide, blood–brain barrier, drug deliveryLin YLHuang XFChang KFLiao KWTsai NMDove Medical Pressarticleglioblastoman-butylidenephthalideblood–brain barrierdrug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 749-760 (2020) |
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glioblastoma n-butylidenephthalide blood–brain barrier drug delivery Medicine (General) R5-920 |
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glioblastoma n-butylidenephthalide blood–brain barrier drug delivery Medicine (General) R5-920 Lin YL Huang XF Chang KF Liao KW Tsai NM Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| description |
Yu-Ling Lin, 1,* Xiao-Fan Huang, 2, 3,* Kai-Fu Chang, 2, 3,* Kuang-Wen Liao, 4–6 Nu-Man Tsai 2, 7 1Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan, Republic of China; 2Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, Republic of China; 3Institute of Medicine of Chung Shun Medical University, Taichung 40201, Taiwan, Republic of China; 4Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan, Republic of China; 5Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30010, Taiwan, Republic of China; 6Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, Republic of China; 7Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Nu-Man TsaiDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, TaiwanTel +886-4-24730022 ext. 12411Fax +886-4-23248171Email numan@csmu.edu.twBackground: n-Butylidenephthalide (BP) has anti-tumor effects on glioblastoma. However, the limitation of BP for clinical application is its unstable structure. A polycationic liposomal polyethylenimine (PEI) and polyethylene glycol (PEG) complex (LPPC) has been developed to encapsulate BP for drug structure protection. The purpose of this study was to investigate the anti-cancer effects of the BP/LPPC complex on glioblastoma in vitro and in vivo.Methods: DBTRG-05MG tumor bearing xenograft mice were treated with BP and BP/LPPC and then their tumor sizes, survival, drug biodistribution were measured. RG2 tumor bearing F344 rats also treated with BP and BP/LPPC and then their tumor sizes by magnetic resonance imaging for evaluation blood–brain barrier (BBB) across and drug therapeutic effects. After treated with BP/LPPC in vitro, cell uptake, cell cycle and apoptotic regulators were analyzed for evaluation the therapeutic mechanism.Results: In athymic mice, BP/LPPC could efficiently suppress tumor growth and prolong survival. In F334 rats, BP/LPPC crossed the BBB and led to tumor shrinkage. BP/LPPC promoted cell cycle arrest at the G 0/G 1 phase and triggered the extrinsic and intrinsic cell apoptosis pathways resulting cell death. BP/LPPC also efficiently suppressed VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 expression.Conclusion: BP/LPPC was rapidly and efficiently transported to the tumor area across the BBB and induced cell apoptosis, anti-angiogenetic and anti-metastatic effects in vitro and in vivo.Keywords: glioblastoma, n-butylidenephthalide, blood–brain barrier, drug delivery |
| format |
article |
| author |
Lin YL Huang XF Chang KF Liao KW Tsai NM |
| author_facet |
Lin YL Huang XF Chang KF Liao KW Tsai NM |
| author_sort |
Lin YL |
| title |
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| title_short |
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| title_full |
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| title_fullStr |
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| title_full_unstemmed |
Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood–Brain Barrier and Suppresses Growth of Glioblastoma |
| title_sort |
encapsulated n-butylidenephthalide efficiently crosses the blood–brain barrier and suppresses growth of glioblastoma |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/d70ca8a6260647eeaed52dae7e9da38e |
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