The Biocompatibility and Security of Magnetic Nanoparticles Fe₃O₄-DNR Used In Hematologic Malignancies Therapy

Abstract 3970

The objective of this paper is to study the biocompatibility and security of self-prepared magnetic nanoparticles Fe₃O₄ (Fe₃O₄-MNPs) loaded with daunorubicin (DNR), which has the potential application in hematologic malignancies therapy. Hemolysis test was carried out to estimate it s blood toxicity; Fe₃O₄-MNPs loaded with DNR were intra peritoneally injected into mouse to calculate the LD₅₀; micronucleus (MN) assay was reckoned to identify its genotoxicity; acute toxicity testing was evaluated its influence to mouse hepatic and renal functions. The result of hemolysis rate (HR) of Fe₃O₄-MNPs loaded with DNR was 2.908%, far less than 5%. Therefore, we concluded that self-prepated Fe₃O₄-MNPs loaded with DNR nanoparticles had no hemolytic reaction, and they consistent with the requirement of hemolytic test of biomaterials. The LD₅₀ of Fe₃O₄-MNPs loaded with DNR nanoparticles to the mice was 1009.71mg/kg (relative content of DNR was 10mg/kg) and the 95% confidence interval was 769.11∼1262.40mg/kg, it had no significant difference compared with LD₅₀ of using DNR only, which data was 8.51mg/kg and the 95% confidence interval was 6.48∼10.37mg/kg, and it had wide safety value circumscription. In micronucleus assay, compared Fe₃O₄-MNPs loaded with DNR nanoparticles experimental groups with negative control group, we found that the result had no significant difference (P > 0. 05) in micronucleus formation rate, while compared experimental groups with positive control group, the result had significant difference (P < 0. 05). The result indicated that Fe3O4 magnetic nanoparticles had no cacogenesis and mutagenesis. Acute toxicity testing showed that mice body weigh of control group, Fe₃O₄-MNPs loaded with DNR nanoparticles experimental group and isodose DNR group had no significant difference in 24h, 48h, and 72h after intra peritoneally injection; they had normal activity, eating and evacuation; toxic reactions such as instability of gait, convulsion, paralysis and respiratory depression were not been found; the alanine transarninase (ALT), blood urea nitrogen (BUN), and creatinine clearance rate (CCr) of Fe₃O₄-MNPs loaded with DNR nanoparticles experimental group was 66.0±28.55u/L, 9.06±1.05mmol/L, and 18.03±1.84umol/L, respectively, which had no significant difference compared with control group and isodose DNR group. From the results of our experiment, we could consider that self-prepared Fe₃O₄-MNPs loaded with DNR nanoparticles is a kind of high biocompatibility and security materials and perhaps is suitable for further application in hematologic malignancies therapy.