title: Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies.
abstract: OBJECTIVE
  The objectives of this research were to assess the biocompatibility of self-assembled Fe(3)O(4) magnetic nanoparticles (MNPs) loaded with daunorubicin (DNR), ie, (Fe(3)O(4)-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 Fe(3)O(4)- MNPs/DNR and a micronucleus assay was undertaken to identify its genotoxicity. Fe(3)O(4)-MNPs/ DNR were injected intraperitoneally into mice to calculate the median lethal dose (LD(50)). 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 Fe(3)O(4)-MNPs/DNR. In the micronucleus assay, there was no significant difference in micronucleus formation rate between the experimental Fe(3)O(4)-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 LD(50) of the Fe(3)O(4)-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 Fe(3)O(4)-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.
  
  
  CONCLUSIONS
  Self-assembled Fe(3)O(4)-MNPs/DNR appear to be highly biocompatible and safe nanoparticles, and may be suitable for further application in the treatment of hematologic malignancies.
authors.affiliation: Department of Hematology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
authors.forename: Lijie
authors.initials: L
authors.lastname: Liu
authors.forename: Guohua
authors.initials: G
authors.lastname: Xia
authors.forename: Hulai
authors.initials: H
authors.lastname: Wei
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Mingming
authors.initials: M
authors.lastname: Yang
authors.forename: Liya
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Xu
authors.forename: Jieyong
authors.initials: J
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests
chemical_list: D001672:Biocompatible Materials; D058185:Magnetite Nanoparticles; D003630:Daunorubicin