In Vivo Assimilation of CuS, Iron Oxide and Iron Oxide@CuS Nanoparticles in Mice: A 6-Month Follow-Up Study

Abstract

Nanoparticles (NPs) are at the leading edge of nanomedicine, and determining their biosafety remains a mandatory precondition for biomedical applications. Herein, we explore the bioassimilation of copper sulfide NPs reported as powerful photo-responsive anticancer therapeutic agents. The nanoparticles investigated present a hollow shell morphology, that can be left empty (CuS NPs) or be filled with an iron oxide flower-like core (iron oxide@CuS NPs), and are compared with the iron oxide nanoparticles only (iron oxide NPs). CuS, iron oxide@CuS and iron oxide NPs were injected in 6-week-old mice, at doses coherent with an antitumoral treatment. Cu and Fe were quantified in the liver, spleen, kidneys, and lungs over 6 months, including the control animals, thus providing endogenous Cu and Fe levels in the first months after animal birth. After intravenous NPs administration, 77.0 ± 3.9% of the mass of Cu injected, and 78.6 ± 3.8% of the mass of Fe, were detected in the liver. In the spleen, we found 3.3 ± 0.6% of the injected Cu and 3.8 ± 0.6% for the Fe. No negative impact was observed on organ weight, nor on Cu or Fe homeostasis in the long term. The mass of the two metals returned to the control values within three months, a result that was confirmed by transmission electron microscopy and histology images. This bioassimilation with no negative impact comforts the possible translation of these nanomaterials into clinical practice.

Different coatings on magnetic nanoparticles dictate their degradation kinetics in vivo for 15 months after intravenous administration in mice

“…Hence, the blood residence time of the MNPs appears to be less than 7 days irrespective of the coating they carry. In fact, 7 days after administration the MNPs had accumulated in the different organs in which they were distributed [ 36 , 57 , 58 ], which led us to analyze the biodistribution of all the MNPs at this time.…”

“…Other studies that monitored the bioassimilation of empty copper sulfide NPs (CuS-NPs) or NPs with a flower-like core of iron oxide (iron oxide@CuS-NPs) finally coated with PEG, showed their accumulation mainly in the liver and spleen following i.v. administration to 6-week-old Balb/C mice [ 96 ]. Regarding the degradation of these particles up to 6 months post-administration, they appeared to remain intact within the liver and spleen in TEM images for up to 7 days post-administration.…”

“…Regarding the degradation of these particles up to 6 months post-administration, they appeared to remain intact within the liver and spleen in TEM images for up to 7 days post-administration. However, 3 months after administration no intact hybrid particles were detected, although structures similar to ferritin were detected that were indicative of their degradation [ 96 ]. Ferritin also appeared here, probably reflecting the degradation of the MNPs although at times that differed from those indicated previously, which might vary for different reasons including the particle coating.…”

Theranostic Role of Iron Oxide Nanoparticle for Treating Renal Anemia: Evidence of Efficacy and Significance by MRI, Histology and Biomarkers

“…Similar findings were reported in a mouse model in which 70 µg of iron oxide nanoparticles were injected intravenously, and serial transmission electron microscopy showed progressive degradation of the particles. An in vivo study showed that the liver reserve of iron increased after the IV IOP injection and returned to standard levels 180 days later [ 38 ]. We found that MR images are a powerful in vivo tool for evaluating iron reserves.…”