Background

Glioma accounts for 80 % of all malignant primary brain tumors with a high mortality rate. Histopathological examination is the current diagnostic methods for glioma, but its invasive surgical interventions can cause cerebral edema or impair neural functioning. Liquid biopsy proves to be an efficient method for glioma detection. However, the blood-brain barrier restricts the number of circulating tumor cells (CTCs) in the bloodstream, posing a challenge for sensitive detection of glioma CTCs. This study aims to use the unique characteristics of nanocomposites and the specificity of Angiopep2 (Ang-2) to develop a method that can sensitively identify glioma CTCs.

Results

Herein, a novel label-free impedimetric biosensor was successfully constructed for glioma CTCs detection by using graphene quantum dots (GQDs)-nanoporous gold (NPG) nanocomposites as the immobilized platform and the Ang-2 protein as biorecognition element. The GQDs was homogeneously assembled onto NPG, resulting in the creation of a novel GQDs-NPG nanocomposite with unique structure and function properties. Due to the high electron transfer efficiency of the GQDs-NPG nanocomposite, the developed biosensor exhibited a wild detection range from 1 to 1 × 10⁶ cell mL⁻¹, with a minimal detection limit of 1 cell mL⁻¹. Additionally, the glioma cell biosensor demonstrated a strong anti-interference ability against multiple cell lines, and the stability of the biosensor remained at 96 % after 21 days of storage. Besides, the quantities of glioma cells detected in human serum samples by the glioma cell biosensor demonstrated outstanding consistency with the standard values added to the samples.

Significance

The study provided a novel GQDs-NPG nanocomposite and an electrochemical biosensor based on GQDs-NPG was firstly developed for glioma CTCs detection. The glioma cell biosensor showed high sensitivity, low detection limit, strong anti-interference ability, and good stability in complex biological matrix. The reliable detection of glioma cell was successfully realized in human serum, providing an excellent option for liquid biopsy of glioma CTCs identification and early diagnosis of glioma diseases.

中文翻译：

---

一种基于石墨烯量子点-纳米多孔金纳米复合材料的无标记电化学生物传感器，用于神经胶质瘤细胞的高灵敏度检测

 背景

神经胶质瘤占所有恶性原发性脑肿瘤的 80%，死亡率高。组织病理学检查是目前神经胶质瘤的诊断方法，但其侵入性手术干预可引起脑水肿或损害神经功能。液体活检被证明是检测神经胶质瘤的有效方法。然而，血脑屏障限制了血液中循环肿瘤细胞 （CTC） 的数量，对胶质瘤 CTC 的灵敏检测构成了挑战。本研究旨在利用纳米复合材料的独特特性和 Angiopep2 （Ang-2） 的特异性来开发一种可以灵敏识别胶质瘤 CTC 的方法。

 结果

在此，以石墨烯量子点 （GQD） -纳米多孔金 （NPG） 纳米复合材料为固定化平台，以 Ang-2 蛋白为生物识别元件，成功构建了一种新型无标记阻抗生物传感器，用于胶质瘤 CTCs 检测。GQDs 均匀组装到 NPG 上，从而产生具有独特结构和功能特性的新型 GQDs-NPG 纳米复合材料。由于 GQDs-NPG 纳米复合材料的高电子转移效率，开发的生物传感器表现出 1 至 1×10 ⁶ 细胞 mL ^-1 的野生检测范围，最小检测限为 1 细胞 mL ^-1 。此外，胶质瘤细胞生物传感器对多种细胞系表现出很强的抗干扰能力，储存 21 天后，生物传感器的稳定性保持在 96%。此外，神经胶质瘤细胞生物传感器在人血清样品中检测到的神经胶质瘤细胞数量与添加到样品中的标准值表现出出色的一致性。

 意义

该研究提供了一种新型 GQDs-NPG 纳米复合材料，并首次开发了基于 GQDs-NPG 的电化学生物传感器用于胶质瘤 CTCs 检测。胶质瘤细胞生物传感器灵敏度高，检出限低，抗干扰能力强，在复杂生物基质中稳定性好。在人血清中成功实现了胶质瘤细胞的可靠检测，为胶质瘤 CTC 的液体活检鉴定和胶质瘤疾病的早期诊断提供了极好的选择。