Superparamagnetic iron oxide nanoparticles for imaging and drug delivery

In the past years, nanoparticle usage and research increased enormously in different fields, especially in the clinical sciences for drug delivery and imaging. Selection of the most suitable type of nanoparticle is not always easy because of a broad material variety and different physicochemical characteristics. Depending on the purpose, the safe usage of nanoparticles in vivo needs to be ensured first to predict and eliminate unwanted effects like agglomeration, loss of function, immune system responses (i.e. inflammation), or toxicity after intravenous application. To guarantee the safe usage of nanoparticles, there are various hazard evaluation strategies for different scenarios for example for nanomedicines. Drug delivery with nanomedicines has advantages like increased absorbability, increased in vivo half-life, and decreased drug dosage needs to reach the same therapeutic effect. Amongst others, superparamagnetic iron oxide nanoparticles (SPIONs) and liposomes are already used as medicinal nanoparticles and are approved from the US Food and Drug Administration (FDA). Examples are Feraheme®, which is a ferumoxytol injection for iron deficiency treatments and Doxil®, a liposomal doxorubicin hydrochloride chemotherapy drug. SPIONs are also used as contrast agents because of their high-dense core and the possibility to synthesize very small diameters below 10 nm, which can even penetrate into smallest fenestrations of i.e. the kidneys. This work is divided into two main parts:
Part one was the analysis of different nanoparticle safety evaluation strategies to propose a new hazard evaluation guideline for intravenously applied nanoparticles. This was part of the NanoREG II European Union’s Horizon 2020 research and innovation program under grant agreement 646221.
Part two started with the synthesis and physicochemical characterization of hybrid nanoparticles made out of SPION cores and liposome coatings. The coatings were differently modified with additions like polyethyleneglycol for increased in vivo half-life or folic acid for renal targeting. Injected into zebrafish (Danio rerio) embryos, their biodistribution and toxicity was analyzed. Various methods like confocal laser scanning microscopy and synchrotron X-ray radiation micro-computed phase-contrast tomography were used and compared with each other. Finally, those hybrid nanoparticles were manipulated in vivo with external magnets to increase phagocytic uptake and also with electromagnetic fields and acoustic waves for controlling the nanoparticles in vivo in terms of agglomeration and rotation.