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

Authors Chen B, Wu Weiwei, Cheng J, Lu Q, Gao F, Xu Wenlin, Shen Huiling, Ding Jiahua, Bao wen, Liu Lijie, Xia G, Wei Hulai, Chen J, Wang X, Yang Mimgming, Yang Liya, Zhu H, Xu C

Published 2 December 2010 Volume 2010:5 Pages 1079—1084

DOI https://doi.org/10.2147/IJN.S15660

Review by Single-blind

Peer reviewer comments 4


Weiwei Wu1,2, Baoan Chen1,2, Jian Cheng1, Jun Wang1,2, Wenlin Xu3, Lijie Liu4, Guohua Xia2, Hulai Wei5, Xuemei Wang6, Mingming Yang2, Liya Yang2, Yi Zhang2, Chuanlu Xu2, Jieyong Li2
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
 

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