Effects of iron oxide nanoparticles as T2-MRI contrast agents on reproductive system in male mice

Abstract

Iron oxide nanoparticles (IONPs)-based contrast agents are widely used for T2-weighted magnetic resonance imaging (MRI) in clinical diagnosis, highlighting the necessity and importance to evaluate their potential systematic toxicities. Although a few previous studies have documented the toxicity concerns of IONPs to major organs, limited data are available on the potential reproductive toxicity caused by IONPs, especially when administrated via intravenous injection to mimic clinical use of MRI contrast agents. Our study aimed to determine whether exposure to IONPs would affect male reproductive system and cause other related health concerns in ICR mice. The mice were intravenously injected with different concentrations IONPs once followed by routine toxicity tests of major organs and a series of reproductive function-related analyses at different timepoints. As a result, most of the contrast agents were captured by reticuloendothelial system (RES) organs such as liver and spleen, while IONPs have not presented adverse effects on the normal function of these major organs. In contrast, although IONPs were not able to enter testis through the blood testicular barrier (BTB), and they have not obviously impaired the overall testicular function or altered the serum sex hormones levels, IONPs exposure could damage Sertoli cells in BTB especially at a relative high concentration. Moreover, IONPs administration led to a short-term reduction in the quantity and quality of sperms in a dose-dependent manner, which might be attributed to the increase of oxidative stress and apoptotic activity in epididymis. However, the semen parameters have gradually returned to the normal range within 14 days after the initial injection of IONPs. Collectively, these results demonstrated that IONPs could cause reversible damage to the reproductive system of male mice without affecting the main organs, providing new guidance for the clinical application of IONPs as T2-MRI contrast agents. Graphical Abstract

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy

“…Owing to their intrinsic magnetic properties and easy functionalization, they are excellent nanostructures for cancer management, being capable of acting as diagnosis and/or therapeutic agents. In fact, iron oxide nanoparticles have been used in clinical practice as contrast agents for magnetic resonance imaging (MRI) [ 1 ]. On the other hand, the therapeutic interest on MNPs relies on the possibility to guide them with a magnetic field gradient to specific tumor locations, enable the controlled release of drugs using drug-loaded MNPs-based nanosystems, and produce local heat under AC magnetic fields (hyperthermia) [ 2 , 3 ].…”

Recent Metal Nanotheranostics for Cancer Diagnosis and Therapy: A Review

“…Most of them reported that IONs enhanced the efficacy of X-ray energies above Fe K-edge more significantly than conventional broadband high-energy X-rays. Although the FDA has approved several ION formulations, specific unwanted toxicity issues reported in many studies that could be overcome by functionalization and surface modification with various coverage and ligands would be helpful to improve their circulation time, clearance, and evasion by reticuloendothelial system, as well as improving tissue targeting, biocompatibility, and stability [74][75][76][77][78]. It has now been demonstrated that [79] the doxorubicin (DOX)-loaded liposomal iron oxide NPs (IONP) (Lipo-IONP/DOX) might serve as a safe and effective agent for combined chemo/photothermal cancer therapy.…”

Ultrasound-driven fabrication of hybrid magnetic tryptophan nanoparticles

“…SPIONs-based contrast agents are widely used for T 2 -weighted MRI in medical diagnosis, [39][40][41] where T 2 is referred to as the transverse relaxation of water in tissues caused by the loss of phase coherence or order among the protons in the transverse plane. Therefore, due to their superparamagnetic nature, MTNs aqueous suspension at 100 mg mL À1 was used to investigate transverse relaxation (T 2 ) and examine their suitability in MRI applications.…”