Safety Evaluation of PEGylated MNPs and p-PEGylated MNPs in SD Rats

Abstract

Abstract Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstratedprominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported.In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD(Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation.Werevealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylatedMNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, butno related pathological change was found. Both MNPs are not mutagenic, while recoverablemild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrateda research approach for the non-clinical safety evaluation of nanoparticles. It also providedcomprehensive valuable safety data for PEGylated and p-PEGylatedMNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications inthe cancer diagnosis and therapy.