Journal
TOXICOLOGY LETTERS
Volume 212, Issue 1, Pages 75-82Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2012.05.009
Keywords
Biocompatibility; Fe3O4; PLLA-PEG-PLLA; Magnetic microspheres; Supercritical CO2
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Funding
- Natural Science Foundation of Fujian Province [2010J05027, 2011J01223]
- National Natural Science Foundation of China [51103049, 81171471, 31170939]
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The biocompatibility of Fe3O4-poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) magnetic microspheres (Fe3O4-PLLA-PEG-PLLA MMPs) prepared in a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS) was evaluated at various levels: cellular, molecular, and integrated. At the cellular level, the investigations of cytotoxicity and intracellular reactive oxygen species (ROS) generation indicate that the polymer-coated MMPs (2.0 mg/mL) had a higher toxicity than uncoated Fe3O4 nanoparticles. which led to about 20% loss of cell viability and an increase (0.2 fold) in ROS generation; the differences were not statistically significant (p > 0.05). However, an opposite phenomenon was observed in tests of hemolysis, which showed that the MMPs displayed the weakest hemolytic activity, namely only about 6% at the highest concentration (20 mg/mL). This phenomenon reveals that polymer-coated MMPs created less toxicity in red blood cells than uncoated Fe3O4 nanoparticles. At the molecular level, the MMPs were shown to be less genotoxic than Fe3O4 nanoparticles by measuring the micronucleus (MN) frequency in CHO-K1 cells. Furthermore, the mRNA expression of pro-inflammatory cytokines demonstrates that polymer-coated MMPs elicited a less intense secretion of pro-inflammatory cytokines than uncoated Fe3O4 nanoparticles. Acute toxicity tests of MMPs show quite a low toxicity, with an LD50 > 1575.00 mg/kg. The evidence of low toxicity presented in the results indicates that the Fe3O4-PLLA-PEG-PLLA MMPs from the SpEDS process have great potential for use in biomedical applications. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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