15纳米金纳米颗粒在图像引导胶质肉瘤放疗中的疗效

Elette Engels, Michael Lerch, Stéphanie Corde, Moeava Tehei
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摘要

有针对性的脑癌治疗是改善长期预后的迫切需要,特别是对于胶质肉瘤和胶质母细胞瘤患者。金纳米粒子(GNPs)具有原子序数高、生物相容性好、体积小等特点,适合癌细胞内化。因此,GNPs是使用图像引导放射治疗改进癌症靶向的理想候选者。本研究研究了15 nm AuroVistTM用于图像引导胶质肉瘤放疗的GNPs,并确定了最佳GNP浓度。通过光学表面等离子体共振吸收,发现GNPs在15 ~ 20 nm之间,流体力学直径为(41.3±0.3)nm。共聚焦成像显示,在24-48 h内,50-500µg/mL的GNPs被很好地内化到9L细胞中。γ-H2AX实验显示,在125和150 kVp x射线照射下,50-500µg/mL的GNPs对9L细胞有放射致敏作用。然而,通过克隆测定,只有500µg/mL的GNPs在150 kVp x射线下产生显著的长期剂量增强(10%存活率时敏化增强比为1.43,50µg/mL时敏化增强比为1.13)。Fischer大鼠9L肿瘤中GNPs的CT成像进一步显示,GNP浓度大于500µg/mL才能区分肿瘤和脑,并在注射后48 h检测GNPs。这些有希望的结果表明,GNPs可用于图像引导x射线放射治疗选择性胶质肉瘤,浓度高于500µg/mL。
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Efficacy of 15 nm Gold Nanoparticles for Image-Guided Gliosarcoma Radiotherapy
Targeted brain cancer treatments are sorely needed to improve long-term prognosis, particularly for gliosarcoma and glioblastoma patients. Gold nanoparticles (GNPs) have unique properties including high atomic number, biocompatibility, and small size for cancer cell internalization. GNPs are consequently an ideal candidate for improved cancer targeting using image-guided radiotherapy. This work investigated 15 nm AuroVistTM GNPs for image-guided gliosarcoma radiotherapy and identified optimum GNP concentrations. The GNPs were found to be 15–20 nm using optical surface plasmon resonance absorption, with a (41.3 ± 0.3) nm hydrodynamic diameter. Confocal imaging showed that 50–500 µg/mL of the GNPs was well-internalized into the 9L cells within 24–48 h. γ-H2AX assays showed that 50–500 µg/mL of the GNPs radiosensitized the 9L cells irradiated with 125 and 150 kVp X-rays. However, only 500 µg/mL of the GNPs produced significant long-term dose enhancement with 150 kVp X-rays (with a sensitization enhancement ratio at 10% survival of 1.43, and 1.13 with 50 µg/mL) using clonogenic assay. CT imaging of the GNPs in the 9L tumors in Fischer rats further showed that GNP concentrations above 500 µg/mL were required to distinguish the tumor from the brain, and the GNPs were detected 48 h after injection. These promising results indicate that the GNPs can be used for selective gliosarcoma treatment with image-guided X-ray radiotherapy at concentrations above 500 µg/mL.
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