Abstract
Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.
Highlights
Characterization by Nuclear Magnetic Resonance (NMR) spectroscopy confirmed that the pure N-Boc-ethylenediamine C4-reversible addition fragmentation chain transfer (RAFT), the protected NH2 end functionalized RAFT agent, was synthesized successfully
We have previously reported that our s-SPIONs enhance the uptake and efficacy of chemotherapeutics in vitro [35]
The broad biodistribution, high stability and rapid clearance of these s-SPIONs confirm their potential for bio-medical applications
Summary
Over the last two decades there has been an increase in the use of magnetic particles and magnetic microspheres including iron oxide nanoparticles (IONPs) and superparamagnetic iron oxide nanoparticles (SPIONs) for bio-medical applications such as imaging, diagnostics, therapies and theranostics, but their suitability for these applications depends on their biodistribution and toxicity profiles [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Ma and co-workers [19] reported that for IP injection of magnetic 35 nm diameter positively charged Fe3O4 nanoparticles from Sigma-Aldrich (Castle Hill, Australia), the safe upper limit was 5 mg/kg administered daily to mice for one week. This equates to a total injection of 35 mg/kg body weight per mouse. This concentration, they observed significant toxicity to both the liver and kidneys with increases in reactive oxygen species (ROS) and changes in the tissue histology. The kidneys showed pronounced distortions in the tubular cell architecture at the highest dose
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