Fighting “Fire with Fire”: Targeted Antioxidant Polymer Nanoparticles Suppress Iron Oxide Nanoparticle Toxicity in Vascular Endothelial Cells.
Owing to their unique imaging and responsive properties, magnetic iron oxide nanoparticles have been of considerable interest as drug carriers and contrast agents for biomedical applications. Recently, however, there has been growing concern on the potential health effects these particles may pose. Iron oxide toxicity has been demonstrated in in vitro and in vivo models, with oxidative stress being implicated as playing a central role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems.