Wang Xiaohui, Li Xinran, Wang Baoquan, Xie Yanxia, Cui Xueru, Jiao Jin, Jiao Jianwei, Zhang Yachao
School of Life Sciences, The Second Affiliated Hospital, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, PR China; College of Life Sciences, Qingdao Agricultural University, Qingdao, 266109, PR China.
School of Life Sciences, The Second Affiliated Hospital, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, PR China.
Anal Chim Acta. 2025 Feb 1;1337:343555. doi: 10.1016/j.aca.2024.343555. Epub 2024 Dec 16.
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.
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 × 10 cell mL, with a minimal detection limit of 1 cell mL. 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.
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.
胶质瘤占所有原发性恶性脑肿瘤的80%，死亡率很高。组织病理学检查是目前胶质瘤的诊断方法，但其侵入性手术干预可导致脑水肿或损害神经功能。液体活检被证明是一种有效的胶质瘤检测方法。然而，血脑屏障限制了血液中循环肿瘤细胞（CTC）的数量，这对胶质瘤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血管活性肠肽2（Ang-2）的特异性来开发一种能够灵敏识别胶质瘤CTC的方法。
在此，通过使用石墨烯量子点（GQDs）-纳米多孔金（NPG）纳米复合材料作为固定平台，血管活性肠肽2蛋白作为生物识别元件，成功构建了一种用于检测胶质瘤CTC的新型无标记阻抗生物传感器。GQDs均匀地组装在NPG上，形成了一种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纳米复合材料具有高电子转移效率，所开发的生物传感器具有1至1×10⁶个细胞/毫升的宽检测范围，最低检测限为1个细胞/毫升。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，在储存21天后生物传感器的稳定性仍保持在96%。此外，胶质瘤细胞生物传感器在人血清样本中检测到的胶质瘤细胞数量与添加到样本中的标准值具有出色的一致性。
本研究提供了一种新型的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CTC检测。该胶质瘤细胞生物传感器在复杂生物基质中表现出高灵敏度、低检测限、强抗干扰能力和良好的稳定性。成功实现了在人血清中可靠检测胶质瘤细胞，为胶质瘤CTC识别的液体活检和胶质瘤疾病的早期诊断提供了一个极佳的选择。
