Ursolic acid nanoparticles for glioblastoma therapy.
Ursolic acid nanoparticles for glioblastoma therapy.
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DOI：
10.1016/j.nano.2023.102684
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发表时间：
2023-04
期刊：
影响因子：
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通讯作者：
Yong Li;Linyao Zhao;Qing Zhao;Youdong Zhou;Long Zhou;Ping Song;Baohui Liu;Qianxue Chen;Gang Deng
中科院分区：
文献类型：
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作者：
Yong Li;Linyao Zhao;Qing Zhao;Youdong Zhou;Long Zhou;Ping Song;Baohui Liu;Qianxue Chen;Gang Deng
多形性胶质母细胞瘤（GBM）是中枢神经系统（CNS）最常见、最致命的原发性肿瘤。由于血脑屏障（BBB）的存在，GBM的化疗效果受到限制。本研究的目的是开发用于GBM治疗的熊果酸（UA）自组装纳米粒。采用免疫印迹分析、荧光染色和流式细胞术等方法探讨UA纳米粒抗胶质母细胞瘤的作用机制。UA纳米颗粒的抗肿瘤作用进一步证实在体内使用颅内异种移植物models.ResultsUA成功制备。在体外实验中，UA纳米颗粒可显著增加裂解型半胱氨酸蛋白酶3和LC 3-II的蛋白水平，通过自噬和凋亡强烈消除胶质母细胞瘤细胞。在颅内移植瘤模型中，UA NPs能有效进入血脑屏障，并能显著提高小鼠的存活时间。结论成功合成了UA NPs，其能有效进入血脑屏障，并具有较强的抗肿瘤作用，在治疗人胶质母细胞瘤方面具有很大的潜力。
BackgroundGlioblastoma multiforme (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). The effect of chemotherapy of GBM is limited due to the existence of blood-brain barrier (BBB). The aim of this study is to develop self-assembled nanoparticles (NPs) of ursolic acid (UA) for GBM treatment.MethodsUA NPs were synthesized by solvent volatilization method. Western blot analysis fluorescent staining and flow cytometry were launched to explore the anti-glioblastoma mechanism of UA NPs. The antitumor effects of UA NPs were further confirmed in vivo using intracranial xenograft models.ResultsUA were successfully prepared. In vitro, UA NPs could significantly increase the protein levels of cleaved-caspase 3 and LC3-II to strongly eliminate glioblastoma cells through autophagy and apoptosis. In the intracranial xenograft models, UA NPs could further effectively enter the BBB, and greatly improve the survival time of the mice.ConclusionsWe successfully synthesized UA NPs which could effectively enter the BBB and show strong anti-tumor effect which may have great potential in the treatment of human glioblastoma.