Biotransformation of magnetic nanoparticles as a function of coating in a rat model

Abstract

Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications.

Effect of Surface Chemistry and Associated Protein Corona on the Long-Term Biodegradation of Iron Oxide Nanoparticles In Vivo

“…2a). 31 The shift of the χ″(T) maximum location towards lower temperatures indicates the transformation of the iron core ( Fig. 2b).…”

Environmental implications and applications of engineered nanoscale magnetite and its hybrid nanocomposites: A review of recent literature

“…The thiolated SPIONs with mercaptosuccinic acid (MSA) and cysteine (Cys) have no toxic effects for stem cells [118]. Long-term in vivo studies in murine models have shown that dimercaptosuccinic acid (DMSA)-coated MNPs accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected [119]. On the other hand, polyethylene glycol (NP-PEG-(NH2)2)-coated MNPs show a delay in the arrival of the particles to the liver tissue.…”

Effect of iron nanoparticles on free radical oxidation process in blood of rats with Pliss lymphosarcoma

“…Такое предположение согласуется с представлениями о том, что в процессе биодеградации наночастицы металлов могут постепенно растворяться и переходить в ионное состояние. Так, в работе [25] было продемонстрировано накопление железа в тканях лёгкого и печени, а также повышение уровня ферритина в плазме после введения нетоксических доз наночастиц оксида железа. Поскольку антиоксидантные функции ЦП и его участие в обороте железа тесно связаны, выявленное нами увеличение активности ЦП можно рассматривать как механизм защиты от ПОЛ в ответ на повышение уровня железа в организме.…”