(346e) Long-Circulating Magnetic Nanoparticles As Platforms for Multifunctional Nanomedicine

Interest in utilizing magnetic nanoparticles (MNP) for biomedical applications has increased considerably over the past two decades. This excitement has been driven in large part by the success of MNPs as contrast agents in magnetic resonance imaging. The recent investigative trend has also turned toward concurrent therapy, giving rise to the MNPs as potential ‘‘theranostics’’. Recently we reported the synthesis of long-circulating polyethylene glycol-modified MNPs (PEG-MNP) suitable for magnetic targeting.  Using a rat model, this work explored the biodistribution of PEG-MNPs in organs of elimination and showed that enhanced magnetic targeting to brain tumors can be achieved due to their improved circulation lifetime. Reductions in liver (~12 fold) and spleen (~2.5 fold) concentrations at 1 hour compared to parent unmodified-MNPs confirm plasma pharmacokinetics observed previously. Time-course biodistribution analysis revealed that concentrations of PEG-MNP in the liver remained considerably lower than those observed for unmodified-MNP throughout their plasma clearance, while it was observed to continually increase in the spleen for up to 60 hrs – a trend visualized with histology. Limited to no uptake of PEG-MNPs was observed in lungs or kidneys. Additionally, with magnetic targeting, the accumulation of PEG-MNPs selectively in brain tumors (1.0% injected dose/g tissue) was 15-fold greater than that of unmodified-MNPs (0.07% injected dose/g tissue).  This enhanced delivery of PEG-MNP to tumors was further confirmed by MRI and histological analyses, which also suggested that the contribution of passive targeting to tissue retention of nanoparticles was limited.  Our exciting results justified the further development of PEG-MNP as a multifunctional platform for nanomedicine.