Synthesis of superparamagnetic FePt nanoparticles and their suppression on the proliferation of brain tumor cells

摘要

Brain tumors (particularly malignant glioma) are highly aggressive tumors of the central nervous system and are resistant to conventional therapies (such as radiation and chemotherapy). Progress in clinical diagnosis and therapy of brain malignant tumors has lagged behind that of other cancers due to the difficulties posed by the blood-brain battier (BBB). The explorations of novel drug delivery systems and techniques penetrating or bypassing effectively the BBB have attracted considerable attention in multi-disciplinary fields (including chemistry, material science, biomedical engineering, and pharmacy, etc). Benefited from understanding of interactions between nanomaterials and biological systems, nanomaterials and nanotechnology have displayed promising potentials in cancer diagnosis and therapy, especially brain malignant tumors. In fact, translocation of various metal and oxide nanoparticles (such as Au, Ag, Cu, Al, MnO and Mn_2O_3, TiO_2, Fe_2O_3, etc) across the BBB has been well documented in the past decades via the olfactory nerve pathway. Superparamagnetic FePt nanoparticles with tunable size, shape and stoichiometric ratio have been successfully synthesized using different thermal decomposition routes and wet chemical reduction routes. Of particular interest to superparamagnetic FePt nanoparticles could be primarily attributed to their promising potentials in biomedical fields. The magnetic moment of FePt nanoparticles up to ca. 1000 emu cc~(-1) is higher than that of commonly used iron oxide (ca. 300-400 emu cc~(-1)), making them valuable candidates for magnetic resonance imaging. Considerable attention has been increasingly focused on the anticancer activity of FePt nanoparticles. FePt@CoS_2 nanoparticles have been reported to display a much lower IC_(50) (35.5±4.7 ng of Pt/mL) on HeLa cells than that of cisplatin (230 ng of Pt/mL) according to MTT assay. In the present studies, water-soluble FePt NPs about 4 nm in diameter and oil-soluble FePt NPs about 6 nm in diameter were facilely synthesized using amino acids and oleic acid/oleylamine as the capping reagents, respectively. The samples were characterized by XRD, XPS, FT-IR and TEM. Furthermore, three typical brain glioma cell lines (human glioma U251 cells, human astrocytoma U87 cells and human neuroglioma H4 cells) were employed as the model for evaluating anticancer potentials of FePt NPs. Cells were treated with FePt NPs at designed doses and incubation times and the suppression on the proliferation of tumor cells by FePt NPs was evaluated by MTT assay. Our results domenstrate that FePt NPs covered with oleic acid/oleylamine displayed significant suppression on the proliferation of different brain glioma cells in a dose- and time-dependent manner. While FePt NPs covered with Cys displayed low or no cytotoxic effect at the same exposed doses and incubation times. The untake of FePt NPs by different cells was confirmed by TEM observation. In conclusion, our results display a primary evidence on the suppression of the proliferation on brain tumor cells by FePt NPs, suggesting a promising potential of FePt NPs as the clinic therapeutic of brain tumors.