U.O. Endocrinology, General Hospital, Livorno, Livorno, Italy.
Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy.
PLoS One. 2022 Jun 15;17(6):e0269603. doi: 10.1371/journal.pone.0269603. eCollection 2022.
Superparamagnetic iron oxide nanoparticles (SPIONs) coated with glucose (Glc-SPIONs) were prepared by a new approach called Metal Vapor Synthesis (MVS) and their morphological/structural features were investigated by transmission electron microscopy (TEM) and dynamic light scattering. TEM analysis revealed the presence of small roundish crystalline iron oxide nanoparticles in the organic amorphous phase of glucose, The particles were distributed in a narrow range (1.5 nm-3.5 nm) with a mean diameter of 2.7 nm. The hydrodynamic mean diameter of the Glc-SPIONs, was 15.5 nm. From 4 mg/mL onwards, there was a constant level of positive contrast in a T1-weighted sequence. In vitro experiments were performed in three cell lines: pancreatic cancer (PSN-1), human thyroid cancer (BCPAP), and human embryonic kidney non-tumor cells. We evaluated GLUT1 expression in each cell line and demonstrated that the exposure time and concentration of the Glc-SPIONs we used did not affect cell viability. PSN-1 cells were the most effective at internalizing Glc-SPIONs. Although significantly higher than the control cells, a lower Fe content was detected BCPAP cells treated with Glc-SPIONs. To confirm the involvement of GLUT1 in Glc-SPIONs internalization, cellular uptake experiments were also conducted by pre-treating cancer cells with specific GLUT1 inhibitors, All the inhibitors reduced the cancer cell uptake of Glc-SPIONs In vivo tests were performed on mice inoculated with Lewis lung carcinoma. Mice were treated with a single i.v. injection of Glc-SPION and our results showed a great bioavailability to the malignant tissue by the i.v. administration of Glc-SPIONs. Glc-SPIONs were efficiently eliminated by the kidney. To the best of our knowledge, our study demonstrates for the first time that Glc-SPIONs prepared with MVS can be electively internalized by tumor cells both in vitro and in vivo by exploiting one of the most universal metabolic anomalies of cancer.
超顺磁性氧化铁纳米粒子（SPIONs）用葡萄糖（Glc-SPIONs）包覆，通过一种新的方法称为金属蒸汽合成（MVS），并通过透射电子显微镜（TEM）和动态光散射来研究其形态/结构特征。TEM 分析显示，在葡萄糖的无定形有机相中存在小而圆的结晶氧化铁纳米粒子，这些粒子分布在较窄的范围内（1.5nm-3.5nm），平均粒径为 2.7nm。Glc-SPIONs 的水动力平均粒径为 15.5nm。从 4mg/ml 开始，在 T1 加权序列中有恒定的正对比水平。在三个细胞系中进行了体外实验：胰腺癌（PSN-1）、人甲状腺癌细胞（BCPAP）和人胚肾非肿瘤细胞。我们评估了每个细胞系中 GLUT1 的表达，并证明我们使用的 Glc-SPIONs 的暴露时间和浓度不会影响细胞活力。PSN-1 细胞是最有效地内化 Glc-SPIONs 的细胞。虽然明显高于对照细胞，但在 Glc-SPIONs 处理的 BCPAP 细胞中检测到较低的 Fe 含量。为了确认 GLUT1 参与 Glc-SPIONs 的内化，还通过用特异的 GLUT1 抑制剂预处理癌细胞进行了细胞摄取实验，所有抑制剂均降低了癌细胞对 Glc-SPIONs 的摄取。在接种 Lewis 肺癌的小鼠中进行了体内试验。用 Glc-SPION 的单次静脉内注射治疗小鼠，我们的结果表明，通过静脉内给予 Glc-SPIONs，对恶性组织有很好的生物利用度。Glc-SPIONs 被肾脏有效清除。据我们所知，我们的研究首次表明，用 MVS 制备的 Glc-SPIONs 可以通过肿瘤细胞的一种最普遍的代谢异常在体内和体外被选择性地内化。
