Synthesis And Characterization Of FePt Nanoparticles And Their Suppression On Glioma Cell Proliferation

Gliomas are primary malignant brain tumors at any age in humans with a survival rate of only5%after five years. Treatment of gliomas faced with severe difficulties although recent improvements in surgery and multimodal adjuvant therapy such as radiation therapy, chemotherapy and photodynamic therapy (PDT). The efficacy of PDT and chemotherapy for brain tumors is limited by the blood-brain barrier (BBB) and can be greatly improved by efficient delivery of the drugs to the specific tumor location. The nanomaterials-based nanotechnology has emerged as promising opportunities for conquering brain malignant gliomas due to the advantages to cross the BBB.Noble metal platinum and their compounds (such as Cisplatin) have been used as powerful anti-cancer agents for many years. Recently, FePt nanoparticles have attracted a great deal of attention in biomedical applications derived from its excellent superparamagnetic property, chemical stability and anti-cancer activity. FePt NPs have therefore been used as the MRI contrast agent for cancer detection and a potent agent to kill many cancer cells. In the present study, FePt NPs with different components and surface coatings were facilely synthesized using oleic acid/oleylamine (OA/OA) and amino acid (cystine, Cys) as the capping reagents, respectively. The products were well characterized through XRD, TEM, XPS, FT-IR, and atomic absorption spectrum (AAS). Furthermore, the anticancer potential of FePt NPs with different components and surface coatings was evaluated through MTT assay using three typical brain tumor cells (human glioma U251cells, human astrocytoma U87cells and human neuroglioma H4cells) as the in vitro models. The uptake of FePt NPs by tumor cells was observed by TEM observation. The results show that the proliferations of brain glioma cells were significantly suppressed in the time-and/or dose-dependent manner by FePt NPs coated with OA/OA, while no or low cytotoxic effects were detected in the case of Cys-coated FePt NPs under the same incubation conditions. With the same surface coating, only slight differences on the suppression of cell proliferation were observed derived from the different components of FePt NPs. The internalization of FePt NPs by glioma cells was confirmed regardless of the components and surface coatings, which involved several phases, including the adsorption of FePt NPs on the outer surface of cell membrane, the caveolae and the formation of vesicles containing the aggregates of FePt NPs, intracellular release of FePt NPs from the vesicles and the penetration of FePt NPs through lipid membranes to enter various organelles (such as cell nuclei and mitochondria, etc). We demonstrate that FePt NPs are capable of releasing Fe and Pt in low pH (4.8) environments, while the releasing is related to compositions and surface coatings.In conclusion, these results suggest that FePt NPs significantly suppressed the proliferation of brain glioma cells dependent on the surface coatings, demonstrating the promising potential as the novel anticancer nanomedicine for clinical therapy of brain malignant gliomas.