Abstract
Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein – namely the ferritin – in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products.
Highlights
Iron oxide nanoparticles (IONPs) found their way into the clinics because they are biodegradable and their products of degradation can be processed by the physiological iron metabolism
Citrate-coated CoIONPs of 8.7 ± 2.9 nm diameter synthesized by coprecipitation method (Figure S1) were injected intravenously in mice at the dose recommended for clinical MRI when using IONPs (50 μmol/kg iron)
Numerous ferritin proteins are observed in the neighborhood of CoIONPs lying within lysosomes (Fig. 1), with similar patterns to what was previously observed after injection of IONPs3–5
Summary
Citrate-coated CoIONPs of 8.7 ± 2.9 nm diameter synthesized by coprecipitation method (Figure S1) were injected intravenously in mice at the dose recommended for clinical MRI when using IONPs (50 μmol/kg iron). Structural and elemental analyses of the exogenous intact or degraded CoIONPs and endogenous ferritin proteins were achieved by HRTEM, STEM-HAADF and energy dispersive X-ray (EDX) nano-analyses performed on single particles at different time-points after injection. STEM-HAADF and EDX analysis confirm the presence of two types of structures: the native cobalt ferrite NPs (8.7 ± 2.9 nm) coexisting with very small NPs (3.3 ± 0.4 nm) which exhibit EDX peaks for iron, cobalt and sulfur at 6.45 KeV, 6.95 KeV and 2.4 KeV, respectively, with relative atomic percentages of 64.7%, 28.2% and 7.13% and with an error of ±1% This result clearly confirms the ability of ApoF to sequester simultaneously iron and cobalt ions coming from the degradation of CoIONPs within a minimal lysosome-like environment
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