Abstract:

BACKGROUND: Ferroferric oxide (Fe₃O₄) nanoparticles are a research hotspot in drug delivery system, which can transport antineoplastic drugs to the lesion under external magnetic field. Additionally, its submicrons even can reach the tumor site several centimeters far away from the magnetic source.
OBJECTIVE: To investigate the histocompatibility and in vivo distribution of Fe₃O₄ nanoparticles and to explore its application prospect and limitations as a drug carrier in the chemotherapy of osteosarcoma.
METHODS: 10.0 mg/kg Fe₃O₄ nanoparticles were administrated into Wistar rats via tail vein, then the rats were executed at 15, 60 and 120 minutes, respectively, and the rat lung, brain, heart, liver, kidney, hind limb and skeletal muscle were removed. The ferric ion content in each tissue was determined by atomic absorption spectrometer, and the morphological changes of different tissues were observed by hematoxylin-eosin staining at each time point.
RESULTS AND CONCLUSION: After administrated for 15 minutes, the concentration of Fe₃O₄ nanoparticles in the liver and kidney reached peak, followed by a decrease at 60 and 120 minutes, but still remained a high level. The concentration of Fe₃O₄ nanoparticles at three time points showed significant difference compared with the control group (P < 0.05), demonstrating that the nanoparticles can be quickly enriched and long-term persistent in the liver and kidney. After administrated for 15 minutes, the concentration of Fe₃O₄ nanoparticles in the heart, lung, skeletal muscle and bone reached peak, which had significant difference compared with the control group (P < 0.05), and significantly decreased subsequently except that in the bone. This significant difference still displayed at 60 minutes between groups (P < 0.05), indicating that the nanoparticle can reach a high concentration but persist short time in the high blood perfused tissues. Compared with the control group, the concentration of Fe₃O₄ nanoparticles in the brain tissue showed no significant difference at each time point (P > 0.05), suggesting that the blood-brain barrier can inhibit the nanoparticle penetration. No overt morphological changes were found in each tissue after hematoxylin-eosin staining. In conclusion, the distribution of Fe₃O₄ nanoparticles conjugate sodium oleate in organism is influenced by the blood perfusion and mononuclear phagocyte system, and they cannot penetrate the blood-brain barrier and make no significant effect on tissues, but maintain a high level in the liver kidney and bone for a long-term, thus providing a theoretical basis for the drug delivery system in the magenetic hyperthermia therapy of malignant tumors.

Key words: Ferrosoferric Oxide, Nanoparticles, Histocompatible Materials, Drug Therapy, Tissue Engineering