ECE2022 Rapid Communications Rapid Communications 6: Endocrine-Related Cancer (8 abstracts)
1U.O. Endocrinology, ASL Nord Ovest Toscana, Livorno, Italy; 2USL Tuscany Northwest, Pisa, Italy; 3University of Pisa, Pisa, Italy; 4University of Padua, Padova, Italy; 5CNR PISA, Pisa, Italy
Background: It is well known that one of the basic characteristics of tumor cells is that they are greedy for glucose. Delivering Glucose Coated Superparamagnetic iron oxide nanoparticles (Glc-SPIONs) to tumor cells by i.v. administration could represent the magic bullet for detecting and treating cancer,
Materials, methods and results: Glc-SPIONs were prepared by a new approach called Metal Vapor Synthesis (MVS) and their structural features were investigated by transmission electron microscopy and dynamic light scattering. Our Glc-SPIONs are homogeneous, with a mean diameter of 2.7 nm, and surrounded by a thick layer of glucose, reaching an apparent hydrodynamic diameter of 13 nm (30). From 4 mg/ml onwards, there was a constant level of positive contrast in a T1-weighted sequence at MRI. In vitro experiments were performed in three cell lines: pancreatic cancer (PSN-1), human papillary thyroid cancer (BCPAP), and human embryonic kidney non-tumor cells (HEK293). Concentration of the Glc-SPIONs we used did not affect cell viability. Glc-SPIONs were internalized in all the cancer cells in a time-dependent manner. PSN-1 cells were the most effective at internalizing Glc-SPIONs. Although significantly higher than the control cells, a lower Fe content was detected in human BCPAP cells treated with Glc-SPIONs. We evaluated GLUT1 expression in each cell line and demonstrated that the exposure time Glc-SPION uptake in the two different cancer cells correlated well with the detected GLUT1 levels, thus suggesting the involvement of GLUT1 in the cellular internalization of Glc-SPIONs. To confirm the involvement of GLUT1 in Glc-SPIONs internalization, cellular uptake experiments were also conducted by pre-treating cancer cells for 1 h with specific GLUT1 inhibitors, namely a polyclonal anti-GLUT1, WZB117, Fasentin, BAY-876, and STF-31. In vivo tests were performed on mice inoculated with Lewis lung carcinoma. Our results showed a great bioavailability to the malignant tissue by the i.v. administration of Glc-SPION while a substantial number of Glc-SPIONs were excreted in the urine 6 h after injection, thus supporting the hypothesis that Glc-SPIONs can be efficiently eliminated by the kidney. Regarding nefrotoxicity treatment with Glc-SPIONs led to a 24 h excretion of uTP, which was three times lower than the one recorded with cisplatin.
Conclusion: 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.