共轭石墨烯量子点在脑肿瘤大鼠模型中的抗癌和神经保护作用

Vimal Patel, Jigar Shah
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摘要

胶质母细胞瘤被认为是一种最复杂和高度恶性的原发性脑肿瘤。通过在大鼠大脑的不同病灶部位直接颅内注射 ENU,建立了快速进展脑肿瘤模型。GQD 采用自下而上的技术合成,并通过碳二亚胺酰胺化活化技术与曲妥珠单抗和 Caspase-8 抗体功能化。所有 GQD 共轭物都在 SK-N-SH 和 N2a 细胞系中进行了体外细胞毒性 MTT 试验。在健康大鼠体内对合成的 GQD 进行了急性和慢性毒性试验,并评估了溶血活性和 CRP 水平。合成的准球形二维微小 GQD 的粒径小于 10 纳米,量子产率为 12.7%。DSL、TEM、AFM、傅立叶变换红外光谱和荧光光谱对 GQD 共轭物进行了表征。GQD 与抗体之间的硅内分子对接符合静态相互作用。GQD 结合物在两种细胞系中均表现出剂量依赖性毒性,在大鼠血液中则表现出轻微的急性毒性。研究人员对患 GBM 肿瘤的大鼠进行了 GQD 结合物的抗癌和神经保护活性评估。组织病理学、免疫组化、代谢和炎症性肿瘤生物标志物评估结果表明,GQD_Caspase-8共轭物的抗肿瘤和神经保护效果优于其他共轭物。
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Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model
Glioblastoma has been recognized as a most complex and highly malignant type of primary brain tumor. The rapid progression brain tumor model was developed by direct intracranial administration of ENU at the different focal brain points in the rat brains. The GQD was synthesized by bottom-up technique and functionalized with Trastuzumab and Caspase-8 antibody by Carbodiimide-amidation activation. The in-vitro cytotoxicity MTT assay was performed with all the GQD conjugates in SK-N-SH and N2a cell lines. The acute and chronic toxicity of synthesized GQD was performed in healthy rats and evaluated the hemolytic activity and CRP levels. A synthesized quasi-spherical 2D tiny GQD has a particle size of less than 10 nm and a 12.7% quantum yield. DSL, TEM, AFM, FTIR, and fluorescence spectroscopy characterized the GQD conjugates. In-silico molecular docking was a conformed static interaction between GQD and antibodies. GQD-conjugates showed dose-dependent toxicity in both cell lines and mild acute toxicity in rat blood. The GBM tumor-bearing rats were assessed for the anticancer and neuroprotective activity of the GQD conjugates. Histopathology, immunohistochemistry, metabolic, and inflammatory tumor biomarker estimation showed that the GQD_Caspase-8 conjugate showed better anti-tumor and neuroprotective effects than other conjugates.
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