Biocompatibility of Fe₃O₄/DNR magnetic nanoparticles in the treatment of hematologic malignancies

Weiwei Wu^1,2, Baoan Chen^1,2, Jian Cheng¹, Jun Wang^1,2, Wenlin Xu³, Lijie Liu⁴, Guohua Xia², Hulai Wei⁵, Xuemei Wang⁶, Mingming Yang², Liya Yang², Yi Zhang², Chuanlu Xu², Jieyong Li^2
1Department of Hematology, ²College of Medicine, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China; ³Department of Hematology, The First People’s Hospital of Zhenjiang, Zhenjiang, People’s Republic of China; ⁴Institution of Physiology, Southeast University, Nanjing; ⁵School of Basic Medical Science, Lanzhou University, Lanzhou, People’s Republic of China; ⁶State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of China

Purpose: The objectives of this research were to assess the biocompatibility of self-assembled Fe₃O₄ magnetic nanoparticles (MNPs) loaded with daunorubicin (DNR), ie, (Fe₃O₄-MNPs/DNR), and to explore their potential application in the treatment of hematologic malignancies.
Methods: A hemolysis test was carried out to estimate the hematologic toxicity of Fe₃O₄-MNPs/DNR and a micronucleus assay was undertaken to identify its genotoxicity. Fe₃O₄-MNPs/DNR were injected intraperitoneally into mice to calculate the median lethal dose (LD₅₀). The general condition of the mice was recorded, along with testing for acute toxicity to the liver and kidneys.
Results: Hemolysis rates were 2.908%, 2.530%, and 2.415% after treatment with different concentrations of Fe₃O₄-MNPs/DNR. In the micronucleus assay, there was no significant difference in micronucleus formation rate between the experimental Fe₃O₄-MNPs/DNR groups and negative controls (P > 0.05), but there was a significant difference between the experimental groups and the positive controls (P > 0.05). The LD₅₀ of the Fe₃O₄-MNPs/DNR was 1009.71 mg/kg and the 95% confidence interval (CI) was 769.11–1262.40 mg/kg, while that of the DNR groups was 8.51 mg/kg (95% CI: 6.48–10.37 mg/kg), suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing showed no significant difference in body weight between the treatment groups at 24, 48, and 72 hours after intraperitoneal injection. The mice were all in good condition, with normal consumption of water and food, and their stools were formed and yellowish-brown. Interestingly, no toxic reactions, including instability of gait, convulsion, paralysis, and respiratory depression, were observed. Furthermore, alanine transaminase, blood urea nitrogen, and creatinine clearance in the experimental Fe₃O₄-MNPs/DNR groups were 66.0 ± 28.55 U/L, 9.06 ± 1.05 mmol/L, and 18.03 ± 1.84 µmol/L, respectively, which was not significantly different compared with the control and isodose DNR groups.
Conclusion: Self-assembled Fe₃O₄-MNPs/DNR appear to be highly biocompatible and safe nanoparticles, and may be suitable for further application in the treatment of hematologic malignancies.

Keywords: magnetic nanoparticles, Fe₃O₄, daunorubicin, biocompatibility, hematologic malignancies, therapy