High grade-gliomas are highly invasive and prone to metastasis, leading to poor survival and prognosis. Currently, we urgently need a new treatment strategy to effectively inhibit glioma. In this study, artemether and paclitaxel were used as two agents for tumour suppression. Two functional materials were synthesised and modified on the surface of the micelle as targeting molecules. The addition of two functional materials confers the ability of the micelles to effectively cross the blood-brain barrier (BBB) and then target the glioma cells. Thus, this dual-targeted delivery system allows the drug to play a better role in inhibiting tumour invasion and vasculogenic mimicry (VM) channels. In this paper, the anticancer effects of dual-targeted artemether plus paclitaxel micelles on glioma U87 cells were studied in three aspects: (I) In vitro and in vivo targeting assessment, including the role of penetrating BBB and targeting glioma; (II) In vitro regulation of invasion-associated proteins; (III) Inhibition of VM channels formation and invasion in vitro; (IV) The study of pharmacodynamics in tumour-bearing mice. These results suggest that dual-targeted artemether plus paclitaxel micelle may provide a new strategy to treat glioma via inhibiting invasive and VM channels.

中文翻译：

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双靶向蒿甲醚加紫杉醇胶束提高浸润性脑胶质瘤的治疗效果。

高度神经胶质瘤是高度侵入性的，易于转移，导致不良的生存和预后。当前，我们迫切需要一种新的治疗策略来有效抑制神经胶质瘤。在这项研究中，蒿甲醚和紫杉醇被用作抑制肿瘤的两种药物。合成了两种功能材料，并在胶束表面修饰了它们作为靶向分子。两种功能材料的添加赋予了胶束有效穿过血脑屏障（BBB）然后靶向神经胶质瘤细胞的能力。因此，这种双重靶向的递送系统使药物在抑制肿瘤侵袭和血管生成模拟（VM）通道方面发挥了更好的作用。本文从三个方面研究了双靶向蒿甲醚加紫杉醇胶束对神经胶质瘤U87细胞的抗癌作用：（I）体外和体内靶向评估，包括穿透血脑屏障和靶向神经胶质瘤的作用；（二）入侵相关蛋白的体外调控；（三）体外抑制VM通道的形成和侵袭；（IV）对荷瘤小鼠药效学的研究。这些结果表明，双靶向蒿甲醚加紫杉醇胶束可能通过抑制侵袭性和VM通道提供了一种治疗脑胶质瘤的新策略。