据报道，xanthone α-mangostin (AMN) 对多形性胶质母细胞瘤 (GBM) 具有细胞毒性活性，GBM 是一种预后不良的侵袭性恶性脑癌。认识到 AMN 的高度疏水性可能会限制其全身给药，我们使用重构的高密度脂蛋白 (rHDL) 纳米颗粒配制 AMN。该配方的光物理特性，包括荧光寿命和稳态各向异性，表明 AMN 已成功掺入 rHDL 纳米颗粒中。据我们所知，这是第一份关于 AMN 与基于 HDL 的药物载体的荧光特性的报告。 LN-229 GBM 细胞和正常人星形胶质细胞的 2D 培养物和 3D 球体模型中的细胞毒性研究表明，与未掺入的 AMN 和标准 GBM 化疗药物替莫唑胺相比，rHDL-AMN 制剂的治疗指数有所提高。此外，与星形胶质细胞相比，rHDL-AMN 处理在 LN-229 细胞中更大程度地促进了自噬和活性氧生成的剂量依赖性上调，表明这种新制剂的脱靶毒性降低。这些研究表明，通过使用 rHDL-AMN 制剂进行选择性靶向治疗，对 GBM 患者具有潜在的治疗益处。

Cytotoxic activity has been reported for the xanthone α-mangostin (AMN) against Glioblastoma multiforme (GBM), an aggressive malignant brain cancer with a poor prognosis. Recognizing that AMN's high degree of hydrophobicity is likely to limit its systemic administration, we formulated AMN using reconstituted high-density lipoprotein (rHDL) nanoparticles. The photophysical characteristics of the formulation, including fluorescence lifetime and steady-state anisotropy, indicated that AMN was successfully incorporated into the rHDL nanoparticles. To our knowledge, this is the first report on the fluorescent characteristics of AMN with an HDL-based drug carrier. Cytotoxicity studies in a 2D culture and 3D spheroid model of LN-229 GBM cells and normal human astrocytes showed an enhanced therapeutic index with the rHDL-AMN formulation compared to the unincorporated AMN and Temozolomide, a standard GBM chemotherapy agent. Furthermore, treatment with the rHDL-AMN facilitated a dose-dependent upregulation of autophagy and reactive oxygen species generation to a greater extent in LN-229 cells compared to astrocytes, indicating the reduced off-target toxicity of this novel formulation. These studies indicate the potential therapeutic benefits to GBM patients via selective targeting using the rHDL-AMN formulation.