Functionalized maghemite nanoparticles for enhanced adsorption of uranium from simulated wastewater and magnetic harvesting.

Maghemite (γ-Fe2O3) nanoparticles (MNPs) were functionalized with 3-aminopropyltriethoxysilane (APTES) to give APTES@Fe2O3 (AMNP) which was then reacted with diethylenetriamine-pentaacetic acid (DTPA) to give a nanohybrid DTPA-APTES@Fe2O3 (DAMNP). Nano-isothermal titration calorimetry shows that DTPA complexation with uranyl ions in water is exothermic and has a stoichiometry of two DTPA to three uranyl ions. Density functional theory calculations indicate the possibility of several complexes between DTPA and UO22+ with different stoichiometries. Interactions between uranyl ions and DAMNP functional groups are revealed by X-photoelectron and Fourier transform infrared spectroscopies. Spherical aberration-corrected Scanning Transmission Electron Microscopy visualizes uranium on the particle surface. Adsorbent performance metrics were evaluated by batch adsorption studies under different conditions of pH, initial uranium concentration and contact time, and the results expressed in terms of equilibrium adsorption capacities (qe) and partition coefficients (PC). By either criterion, performance increases from MNP to AMNP to DAMNP, with the maximum uptake at pH 5.5 in all cases: MNP, qe = 63 mg g-1, PC = 127 mg g-1 mM-1; AMNP, qe = 165 mg g-1, PC = 584 mg g-1 mM-1; DAMNP, qe = 249 mg g-1, PC = 2318 mg g-1 mM-1 (at 25 °C; initial U concentration 0.63 mM; 5 mg adsorbent in 10 mL of solution; contact time, 3 h). The pH maximum is related to the predominance of mono- and di-cationic uranium species. Uptake by DAMNPs follows a pseudo-first-order or pseudo-second-order kinetic model and fits a variety of adsorption models. The maximum adsorption capacity for DAMNPs is higher than for other functionalized magnetic nanohybrids. This adsorbent can be regenerated and recycled for at least 10 cycles with less than 10% loss in activity, and shows high selectivity. These findings suggest that DAMNP could be a promising adsorbent for the recovery of uranium from nuclear wastewaters.

Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells.

While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells' differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Using magnetism as a fingerprint of the transformation process, we evidenced an important degradation of the nanoparticles during chondrogenesis. For the other pathways, stem cells were remarkably "remagnetized" after degradation of nanoparticles. This remagnetization phenomenon is the direct demonstration of a possible neosynthesis of magnetic nanoparticles in cellulo and could lay some foundation to understand the presence of magnetic crystals in human cells. The neosynthesis was shown to take place within the endosomes and to involve the H-subunit of ferritin. Moreover, it appeared to be the key process to avoid long-term cytotoxicity (impact on differentiation) related to high doses of magnetic nanoparticles within stem cells.

New Iron Oxide Nanoparticles Catechol-Grafted with Bis(amidoxime)s for Uranium(VI) Depletion of Aqueous Solution.

Environmental pollution caused by heavy metals constitutes a serious public health problem. In the case of uranium depletion, amidoxime groups are important because of their high affinity for uranium(VI). New series of bis(amidoxime)s with catechol-derived anchor groups were tested (b-AMD-1 and b-AMD-2). The catechol groups were designed to bind to the surface of maghemite nanoparticles (MNPs), and two nanohybrid devices MNP-b-AMD-1 and MNP-b-AMD-2 were obtained. This strategy makes for efficient removal of U(VI) via its complexation with the bis(amidoxime)s (b-AMD) and also its extraction from aqueous solution by magnetic harvesting of the MNPs. The assynthesized and b-AMD-grafted MNPs were characterized by several techniques: X-ray diffraction (XRD), high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM), X-ray photoelectron spectrophotometry (XPS), thermal analysis (TG/DTA) and Fourier transform infrared spectroscopy (FTIR). Sorption tests were run at pH 6.5, which corresponds to the highest affinity and selectivity of b-AMD for U(VI). After magnetic separation, the chelation ability and the selectivity of MNP-b-AMD-1 and MNP-b-AMD-2 towards U(VI) were evaluated by measuring the residual U(VI) concentration in the supernatant by inductively coupled plasma-mass spectrometry (ICP-MS). The data were plotted according to the Langmuir and Freundlich isotherms; the maximal sorption capacity (qmax) was 29 and 60 mg U g-1 for MNP-b-AMD-1 and MNP-b-AMD-2, respectively. This confirms that bis(amidoxime) groups are good candidates for uranium depletion of aqueous solution.

Ferritin Protein Regulates the Degradation of Iron Oxide Nanoparticles.

Proteins implicated in iron homeostasis are assumed to be also involved in the cellular processing of iron oxide nanoparticles. In this work, the role of an endogenous iron storage protein-namely the ferritin-is examined in the remediation and biodegradation of magnetic iron oxide nanoparticles. Previous in vivo studies suggest the intracellular transfer of the iron ions released during the degradation of nanoparticles to endogenous protein cages within lysosomal compartments. Here, the capacity of ferritin cages to accommodate and store the degradation products of nanoparticles is investigated in vitro in the physiological acidic environment of the lysosomes. Moreover, it is questioned whether ferritin proteins can play an active role in the degradation of the nanoparticles. The magnetic, colloidal, and structural follow-up of iron oxide nanoparticles and proteins in lysosome-like medium confirms the efficient remediation of potentially harmful iron ions generated by nanoparticles within ferritins. The presence of ferritins, however, delays the degradation of particles due to a complex colloidal behavior of the mixture in acidic medium. This study exemplifies the important implications of intracellular proteins in processes of degradation and metabolization of iron oxide nanoparticles.

Iron uptake and transfer from ceruloplasmin to transferrin.

BACKGROUND: Dietary and recycled iron are in the Fe(2+) oxidation state. However, the metal is transported in serum by transferrin as Fe(3+). The multi-copper ferroxidase ceruloplasmin is suspected to be the missing link between acquired Fe(2+) and transported Fe(3+). METHODS: This study uses the techniques of chemical relaxation and spectrophotometric detection. RESULTS: Under anaerobic conditions, ceruloplasmin captures and oxidizes two Fe(2+). The first uptake occurs in domain 6 (<1ms) at the divalent iron-binding site. It is accompanied by Fe(2+) oxidation by Cu(2+)D6. Fe(3+) is then transferred from the binding site to the holding site. Cu(+)D6 is then re-oxidized by a Cu(2+) of the trinuclear cluster in about 200ms. The second Fe(2+) uptake and oxidation involve domain 4 and are under the kinetic control of a 200s change in the protein conformation. With transferrin and in the formed ceruloplasmin-transferrin adduct, two Fe(3+) are transferred from their holding sites to two C-lobes of two transferrins. The first transfer (~100s) is followed by conformation changes (500s) leading to the release of monoferric transferrin. The second transfer occurs in two steps in the 1000-10,000second range. CONCLUSION: Fe(3+) is transferred after Fe(2+) uptake and oxidation by ceruloplasmin to the C-lobe of transferrin in a protein-protein adduct. This adduct is in a permanent state of equilibrium with all the metal-free or bounded ceruloplasmin and transferrin species present in the medium. GENERAL SIGNIFICANCE: Ceruloplasmin is a go-between dietary or recycled Fe(2+) and transferrin transported Fe(3+).

Transferrin receptor-1 iron-acquisition pathway - synthesis, kinetics, thermodynamics and rapid cellular internalization of a holotransferrin-maghemite nanoparticle construct.

BACKGROUND: Targeting nanoobjects via the iron-acquisition pathway is always reported slower than the transferrin/receptor endocytosis. Is there a remedy? METHODS: Maghemite superparamagnetic and theragnostic nanoparticles (diameter 8.6nm) were synthesized, coated with 3-aminopropyltriethoxysilane (NP) and coupled to four holotransferrin (TFe2) by amide bonds (TFe2-NP). The constructs were characterized by X-ray diffraction, transmission electron microscopy, FTIR, X-ray Electron Spectroscopy, Inductively Coupled Plasma with Atomic Emission Spectrometry. The in-vitro protein/protein interaction of TFe2-NP with transferrin receptor-1 (R1) and endocytosis in HeLa cells were investigated spectrophotometrically, by fast T-jump kinetics and confocal microscopy. RESULTS: In-vitro, R1 interacts with TFe2-NP with an overall dissociation constant KD=11nM. This interaction occurs in two steps: in the first, the C-lobe of the TFe2-NP interacts with R1 in 50µs: second-order rate constant, k1=6×10(10)M(-1)s(-1); first-order rate constant, k-1=9×10(4)s(-1); dissociation constant, K1d=1.5µM. In the second step, the protein/protein adduct undergoes a slow (10,000s) change in conformation to reach equilibrium. This mechanism is identical to that occurring with the free TFe2. In HeLa cells, TFe2-NP is internalized in the cytosol in less than 15min. CONCLUSION: This is the first time that a nanoparticle-transferrin construct is shown to interact with R1 and is internalized in time scales similar to those of the free holotransferrin. GENERAL SIGNIFICANCE: TFe2-NP behaves as free TFe2 and constitutes a model for rapidly targeting theragnostic devices via the main iron-acquisition pathway.

Dual-Probe SERS Nanosensor: A Promising Approach for Sensitive and Ratiometric Detection of Glucose in Clinical Settings.

Diabetes is a major global health concern, with millions of annual deaths. Monitoring glucose levels is vital for clinical management, and urine samples offer a noninvasive alternative to blood samples. Optical techniques for urine glucose sensing have gained notable traction due to their cost-effectiveness and portability. Among these methods, surface-enhanced Raman spectroscopy (SERS) has attracted considerable attention thanks to its remarkable sensitivity and multiplexing capabilities. However, challenges remain in achieving reliable quantification through SERS. In this study, an alternative approach is proposed to enhance quantification involving the use of dual probes. Each probe is encoded with unique SERS signatures strategically positioned in the biologically silent region. One probe indicates the glucose presence, while the other acts as an internal reference for calibration. This setup enables ratiometric analysis of the SERS signal, directly correlating it with the glucose concentration. The fabrication of the sensor relies on the prefunctionalization of Fe sheets using an aryl diazonium salt bearing a -C≡CH group (internal reference), followed by the immobilization of Ag nanoparticles modified with an aryl diazonium salt bearing a -B(OH)2 group (for glucose capture). A secondary probe bearing a -B(OH)2 group on one side and a -C≡N group on the other side enables the ratiometric analysis by forming a sandwich-like structure in the presence of glucose (glucose indicator). Validation studies in aqueous solutions and artificial urine demonstrated the high spectral stability and the potential of this dual-probe nanosensor for sensitive glucose monitoring in clinical settings.

Uptake and release of metal ions by transferrin and interaction with receptor 1.

BACKGROUND: For a metal to follow the iron acquisition pathway, four conditions are required: 1-complex formation with transferrin; 2-interaction with receptor 1; 3-metal release in the endosome; and 4-metal transport to cytosol. SCOPE OF THE REVIEW: This review deals with the mechanisms of aluminum(III), cobalt(III), uranium(VI), gallium(III) and bismuth(III) uptake by transferrin and interaction with receptor 1. MAJOR CONCLUSIONS: The interaction of the metal-loaded transferrin with receptor 1 takes place in one or two steps: a very fast first step (µs to ms) between the C-lobe and the helical domain of the receptor, and a second slow step (2-6h) between the N-lobe and the protease-like domain. In transferrin loaded with metals other than iron, the dissociation constants for the interaction of the C-lobe with TFR are in a comparable range of magnitudes 10 to 0.5µM, whereas those of the interaction of the N-lobe are several orders of magnitudes lower or not detected. Endocytosis occurs in minutes, which implies a possible internalization of the metal-loaded transferrin with only the C-lobe interacting with the receptor. GENERAL SIGNIFICANCE: A competition with iron is possible and implies that metal internalization is more related to kinetics than thermodynamics. As for metal release in the endosome, it is faster than the recycling time of transferrin, which implies its possible liberation in the cell. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.

Accurate and Ultrafast Simulation of Molecular Recognition and Assembly on Metal Surfaces in Four Dimensions.

Understanding molecular interactions with metal surfaces in high reliability is critical for the development of catalysts, sensors, and therapeutics. Obtaining accurate experimental data for a wide range of surfaces remains a critical bottleneck and quantum-mechanical data remain speculative due to high uncertainties and limitations in scale. We report molecular dynamics simulations of adsorption energies and assembly of organic molecules on elemental metal surfaces using the INTERFACE force field (IFF). The force field-based simulations reach up to 8 times higher accuracy than density functional calculations at a million-fold faster speed, as well as more than 1 order of magnitude higher accuracy than other force fields relative to accurate measurements by single-crystal adsorption calorimetry. Uncertainties of prior computational methods are effectively reduced from on the order of 100% to less than 10% and validated by experimental data from multiple sources. Specifically, we describe the molecular interactions of benzene and naphthalene with even and defective platinum surfaces across a wide range of surface coverage in depth. We discuss molecular-scale influences on the heat of adsorption and clarify the definition of surface coverage. The methods can be applied to 18 metals to accurately predict binding and assembly of organic molecules, ligands, electrolytes, biological molecules, and gases without additional fit parameters.

Recent advances in nanotechnology for eradicating bacterial biofilm.

Microorganisms grouped together into spatially-organized communities called biofilms, are the cause of dramatic chronic infections in plants, animals and humans. In this review, the characteristics of biofilms and their interactions with antimicrobials are first described. Limitations of antibiotic treatments are discussed, and state-of-the-art alternative approaches based on the use of polymer, lipid, organic, inorganic and hybrid nanoparticles are presented, highlighting recent achievements in the application of nanomaterials to the field of theranostics for the eradication of biofilm. The aim of this review is to present a complete vision of nanobiotechnology-based approaches for eradicating bacterial biofilms and fighting antimicrobial tolerance.

Supramolecular organization and biological interaction of squalenoyl siRNA nanoparticles.

Small interfering RNAs (siRNA) are attractive and powerful tools to inhibit the expression of a targeted gene. However, their extreme hydrophilicities combined with a negative charge and short plasma half-life counteract their use as therapeutics. Previously, we chemically linked siRNA to squalene (SQ) which self-assembled as nanoparticles (NPs) with pharmacological efficiency in cancers and recently in a hereditary neuropathy. In order to understand the siRNA-SQ NP assembly and fate once intravenously injected, the present study detailed characterization of siRNA-SQ NP structure and its interaction with serum components. From SAXS and SANS analysis, we propose that the siRNA-SQ bioconjugate self-assembled as 11-nm diameter supramolecular assemblies, which are connected one to another to form spherical nanoparticles of around 130-nm diameter. The siRNA-SQ NPs were stable in biological media and interacted with serum components, notably with albumin and LDL. The high specificity of siRNA to decrease or normalize gene expression and the high colloidal stability when encapsulated into squalene nanoparticles offer promising targeted therapy with wide applications for pathologies with gene expression dysregulation.

Grafting TRAIL through Either Amino or Carboxylic Groups onto Maghemite Nanoparticles: Influence on Pro-Apoptotic Efficiency.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine superfamily. TRAIL is able to induce apoptosis through engagement of its death receptors DR4 and DR5 in a wide variety of tumor cells while sparing vital normal cells. This makes it a promising agent for cancer therapy. Here, we present two different ways of covalently grafting TRAIL onto maghemite nanoparticles (NPs): (a) by using carboxylic acid groups of the protein to graft it onto maghemite NPs previously functionalized with amino groups, and (b) by using the amino functions of the protein to graft it onto NPs functionalized with carboxylic acid groups. The two resulting nanovectors, NH-TRAIL@NPs-CO and CO-TRAIL@NPs-NH, were thoroughly characterized. Biological studies performed on human breast and lung carcinoma cells (MDA-MB-231 and H1703 cell lines) established these nanovectors are potential agents for cancer therapy. The pro-apoptotic effect is somewhat greater for CO-TRAIL@NPs-NH than NH-TRAIL@NPs-CO, as evidenced by viability studies and apoptosis analysis. A computational study indicated that regardless of whether TRAIL is attached to NPs through an acid or an amino group, DR4 recognition is not affected in either case.

In vitro interaction between ceruloplasmin and human serum transferrin.

The thermodynamics of the interactions of serum apotransferrin (T) and holotransferrin (TFe(2)) with ceruloplasmin (Cp), as well as those of human lactoferrin (Lf), were assessed by fluorescence emission spectroscopy. Cp interacts with two Lf molecules. The first interaction depends on pH and µ, whereas the second does not. Dissociation constants were as follows: K(11Lf) = 1.5 ± 0.2 µM, and K(12Lf) = 11 ± 2 µM. Two slightly different interactions of T or TFe(2) with Cp are detected for the first time. They are both independent of pH and µ and occur with 1:1 stoichiometry: K(1T) = 19 ± 7 µM, and K(1TFe2) = 12 ± 4 µM. These results can improve our understanding of the probable process of the transfer of iron from Cp to T in iron and copper transport and homeostasis.

Can uranium follow the iron-acquisition pathway? Interaction of uranyl-loaded transferrin with receptor 1.

Transferrin receptor 1 (R(D)) binds iron-loaded transferrin and allows its internalization in the cytoplasm. Human serum transferrin also forms complexes with metals other than iron, including uranium in the uranyl form (UO(2)(2+)). Can the uranyl-saturated transferrin (TUr(2)) follow the receptor-mediated iron-acquisition pathway? In cell-free assays, TUr(2) interacts with R(D) in two different steps. The first is fast, direct rate constant, k(1) = (5.2 +/- 0.8) x 10(6) M(-1) s(-1); reverse rate constant, k(-1) = 95 +/- 5 s(-1); and dissociation constant K(1) = 18 +/- 6 microM. The second occurs in the 100-s range and leads to an increase in the stability of the protein-protein adduct, with an average overall dissociation constant K(d) = 6 +/- 2 microM. This kinetic analysis implies in the proposed in vitro model possible but weak competition between TUr(2) and the C-lobe of iron-loaded transferrin toward the interaction with R(D).

Author Correction: Tissue damage from neutrophil-induced oxidative stress in COVID-19.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia.

Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or TRAIL-receptor-deficient (DKO), by combining complementary methylene blue assay and flow cytometry detection of apoptosis and necrosis. Results: Combined with MHT or PT under conditions of "moderate hyperthermia" at low concentrations, NC@TRAIL acts synergistically with the TRAIL receptor to increase the cell death rate beyond what can be explained by the mere global elevation of temperature. In contrast, all results are consistent with the idea that there are hotspots, close to the nanovector and, therefore, to the membrane receptor, which cause disruption of the cell membrane. Furthermore, nanovectors targeting other membrane receptors, unrelated to the TNF superfamily, were also found to cause tumor cell damage upon PT. Indeed, functionalization of NCs by transferrin (NC@Tf) or human serum albumin (NC@HSA) induces tumor cell killing when combined with PT, albeit less efficiently than NC@TRAIL. Conclusions: Given that magnetic nanoparticles can easily be functionalized with molecules or proteins recognizing membrane receptors, these results should pave the way to original remote-controlled antitumoral targeted thermal therapies.

Kinetics and thermodynamics of metal-loaded transferrins: transferrin receptor 1 interactions.

Transferrin receptor 1 (R) and human serum transferrin (T) are the two main actors in iron acquisition by the cell. R binds TFe(2) (iron-loaded transferrin), which allows its internalization in the cytoplasm by endocytosis. T also forms complexes with metals other than iron. In order to follow the iron-acquisition pathway, these metals should obey at least two essential rules: (i) formation of a strong complex with T; and (ii) interaction of this complex with R. In the present paper, we propose a general mechanism for the interaction of five metal-loaded Ts [Fe(III), Al(III), Bi(III), Ga(III) and Co(III)] with R and we discuss their potential incorporation by the iron-acquisition pathway. With iron- and cobalt-loaded Ts, the interaction of R takes place in two steps: the first is detected by the T-jump technique and occurs in the 100 micros range, whereas the second is slow and occurs in the hour range. Bi(III)- and Ga(III)-loaded Ts interact with R in a single fast kinetic step, which occurs in the 100-500 micros range. No interaction is detected between R and aluminium-saturated T. The fast steps are ascribed to the interaction of the C-lobe of metal-loaded T with the helical domain of R: dissociation constant, K'(1), of 0.50+/-0.07, 0.82+/-0.25, 4+/-0.4 and 1.10+/-0.12 microM for Fe(III), Co(III), Bi(III) and Ga(III) respectively. The second slow steps are ascribed to changes in the conformation of the protein-protein adducts which increase the stability to achieve, at thermodynamic equilibrium, an overall dissociation constant, K(1), of 2.3 and 25 nM for Fe(III) and Co(III) respectively. This last step occurs over several hours, whereas endocytosis takes place in several minutes. This implies that metal-loaded Ts are internalized with only the C-lobe interacting with R. This suggests that, despite a lower affinity for R when compared with TFe(2), some metal-loaded Ts can compete kinetically with TFe(2) for the interaction with R and thus follow the iron-acquisition pathway.

The mechanism of iron release from the transferrin-receptor 1 adduct.

We report the determination in cell-free assays of the mechanism of iron release from the N-lobe and C-lobe of human serum transferrin in interaction with intact transferrin receptor 1 at 4.3< or =pH< or =6.5. Iron is first released from the N-lobe in the tens of milliseconds range and then from the C-lobe in the hundreds of seconds range. In both cases, iron loss is rate-controlled by slow proton transfers, rate constant for the N-lobe k(1)=1.20(+/-0.05)x10(6)M(-1)s(-1) and for the C-lobe k(2)=1.6(+/-0.1)x10(3)M(-1)s(-1). This iron loss is subsequent to a fast proton-driven decarbonation and is followed by two proton gains, (pK(1a))/2=5.28 per proton for the N-lobe and (pK(2a))/2=5.10 per proton for the C-lobe. Under similar experimental conditions, iron loss is about 17-fold faster from the N-lobe and is at least 200-fold faster from the C-lobe when compared to holotransferrin in the absence of receptor 1. After iron release, the apotransferrin-receptor adduct undergoes a slow partial dissociation controlled by a change in the conformation of the receptor; rate constant k(3)=1.7(+/-0.1)x10(-3)s(-1). At endosomic pH, the final equilibrated state is attained in about 1000 s, after which the free apotransferrin, two prototropic species of the acidic form of the receptor and apotransferrin interacting with the receptor coexist simultaneously. However, since recycling of the vesicle containing the receptor to the cell surface takes a few minutes, the major part of transferrin will still be forwarded to the biological fluid in the form of the apotransferrin-receptor protein-protein adduct.

Cyanobacteria as bioreactors for the synthesis of Au, Ag, Pd, and Pt nanoparticles via an enzyme-mediated route.

Common Anabaena, Calothrix, and Leptolyngbya cyanobacteria are shown to form Au, Ag, Pd, and Pt nanoparticles of well-controlled size. These nanoparticles are synthesized intra-cellularly, and naturally released in the culture medium, where they are stabilized by algal polysaccharides, allowing their easy recovery. The size of the recovered particles as well as the reaction yield is shown to depend on the cyanobacteria genus. Investigations of nanoparticle formation indicate that the intracellular nitrogenase enzyme is responsible for the metal reduction but that the cellular environment is involved in the colloid growth process.

Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin.

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.