標題: Encapsulated n-Butylidenephthalide Efficiently Crosses the Blood-Brain Barrier and Suppresses Growth of Glioblastoma
作者: Lin, Yu-Ling
Huang, Xiao-Fan
Chang, Kai-Fu
Liao, Kuang-Wen
Tsai, Nu-Man
生物科技學系
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
關鍵字: glioblastoma;n-butylidenephthalide;blood-brain barrier;drug delivery
公開日期: 1-Jan-2020
摘要: Background: 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.
URI: http://dx.doi.org/10.2147/IJN.S235815
http://hdl.handle.net/11536/153785
ISSN: 1178-2013
DOI: 10.2147/IJN.S235815
期刊: INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume: 15
起始頁: 749
結束頁: 760
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