Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan.
Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan; Graduate Institute of Medicine, Yuan Ze University, Chung-Li, Taoyuan, Taiwan; Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan.
J Pediatr Surg. 2021 Jul;56(7):1227-1232. doi: 10.1016/j.jpedsurg.2021.03.035. Epub 2021 Mar 24.
Patients with neuroblastoma, a common childhood malignancy, often have poor prognosis. It is mandatory to develop an accurate and efficient diagnostic tool for neuroblastomas, so that the treatment can be started early. Graphene quantum dot (GQD), a nanomaterial, can be used to carry proteins, genetic materials, or drugs. GD2, a disialoganglioside, is a surface antigen expressed on neuroblastoma. This study investigated the in vivo targeting and imaging of neuroblastomas using GD2-targeting GQDs.
GQDs were synthesized and conjugated with anti-GD2 antibody (anti-GD2/GQDs). In vitro cytotoxicity of GQDs and anti-GD2/GQDs was studied in human neuroblastoma cells by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay. The tumor tracking and imaging of anti-GD2/GQDs in mice were investigated by in vivo imaging system (IVIS).
Treatment with GQDs or anti-GD2/GQDs induced no or mild cytotoxicity in fibroblasts and neuroblastoma cells. After co-incubation, GQDs and anti-GD2/GQDs were located in the cytoplasm and nucleus of neuroblastoma cells, with GQDs showing a blue fluorescence and anti-GD2/GQDs an orange/red emission. The IVIS images demonstrated accumulation of the fluorescence of anti-GD2/GQDs in the subcutaneous tumors in mice 24 h after intravenous injection of anti-GD2/GQDs.
Anti-GD2/GQDs may potentially be used for the targeting and imaging of neuroblastomas in vivo.
神经母细胞瘤是一种常见的儿童恶性肿瘤，患者预后往往较差。因此，开发一种准确、高效的神经母细胞瘤诊断工具非常必要，以便能够尽早开始治疗。石墨烯量子点（GQD）是一种纳米材料，可用于携带蛋白质、遗传物质或药物。GD2 是一种二唾液酸神经节苷脂，是神经母细胞瘤表面的一种抗原。本研究使用靶向 GD2 的 GQD 对神经母细胞瘤进行体内靶向和成像研究。
合成 GQD 并与抗 GD2 抗体（抗-GD2/GQDs）偶联。通过 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐比色法研究 GQD 和抗-GD2/GQDs 在人神经母细胞瘤细胞中的体外细胞毒性。通过体内成像系统（IVIS）研究抗-GD2/GQDs 在小鼠中的肿瘤追踪和成像。
GQD 或抗-GD2/GQDs 处理对成纤维细胞和神经母细胞瘤细胞无或仅有轻微的细胞毒性。共孵育后，GQD 位于神经母细胞瘤细胞的细胞质和细胞核中，呈蓝色荧光，而抗-GD2/GQD 则呈橙色/红色发射。IVIS 图像显示，在静脉注射抗-GD2/GQD 后 24 小时，抗-GD2/GQD 在小鼠皮下肿瘤中的荧光积聚。
抗-GD2/GQD 可能可用于体内神经母细胞瘤的靶向和成像。
