1. Introduction
33.4. Future perspectives
3.4.5. Investigations on uptake and effects of iron oxide nanoparticles in vivo
The most important aspect for risk assessment and investigations on therapeutic potential of IONPs in biomedical application are in vivo studies. Though some publications suggest entry of IONPs into brain through the intact BBB (Jain et al., 2008; Wang et al., 2010; Yan et al., 2013), the data are not so clear due to limited resolution of the published microscopic images. Hence, different application modes should be used to investigate possible routes of entry, the amount of iron reaching the brain, and a time dependent distribution of IONPs within the brain. For such studies, fluorescent IONPs should be applied intravenously, intracerebrally or intranasally in rodents and the IONPs in brain and other tissues could be visualized in slices by fluorescence microscopy coupled with immunocytochemical staining, by Perls’ iron staining and/or by TEM after certain incubation periods.
For the brain, parameters of toxicity such as ROS generation or apoptosis as well as changes in morphology of the neural cell types should be analyzed after an IONP exposure, e.g. if microglia turned into the activated state as reported in mice after
intranasal application (Wang et al., 2011a). Moreover, behavioral studies on rats or mice are highly warranted to investigate whether IONP exposure may have a long-term effect on cognition since data on that issue are scarce (chapter 1.4). In order to study whether an altered neural iron content in IONP-treated brains promote neurodegenerative disorders, application of IONPs to animal models for Alzheimer’s and Parkinson’s disease (Bove and Perier, 2012; Dujardin et al., 2014) would be an option. In this context, analysis of the brain from IONP-treated animals for pathological alterations and characteristics of the neurodegenerative disorders should be performed.
In addition to potential adverse effects, IONPs might also be beneficial when applied as drug delivery system. As vehicle for therapeutics, IONPs may be used to treat disorders such as Alzheimer’s or Parkinson’s disease as reported recently for functionalized carbon nanotubes (Professor Dr. Kostas Kostarelos, personal communication). Iron deficiency in brain which causes disorders like restless legs syndrome is not easy to treat by peripheral application of low molecular weight iron due to poor permeability of the brain for iron (Hare et al., 2013). Due to the possibility to functionalize IONPs for good permeation of the BBB into the brain, IONPs might also be a valuable tool to treat iron deficiency.
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4. A Appendix
4.1. Curriculum vitae ... 115 4.2. List of publications ... 117