Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells.

BACKGROUND: The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. METHODS: Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. RESULTS: Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD(50)) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe3O4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe3O4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe3O4 nano magnetofluid concentration. CONCLUSION: The Fe3O4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.

Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.

BACKGROUND: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide (188)Re-labeled folic acid ligand ((188)Re-folate-CDDP/HSA). METHODS: Human serum albumin was labeled with (188)Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of (188)Re-folate-CDDP/HAS magnetic nanoparticles was assessed. RESULTS: Optimal conditions for (188)Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and (188)ReO(4) eluent (0.1 mL). The rate of (188)Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the (188)Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of (188)Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo. CONCLUSION: These results indicate that (188)Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide ((188)Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.