“…The tetrahedral phosphonic groups in this complex limit the free space around the central metal atoms, which are shielded from interacting with ligands in biological environment such as protons, biomolecules, etc . Since EDTMP was reported to have strong binding affinity with heavy metal ions [30–32], this coating may be used for a broad spectrum of toxic MOx to provide stable inert surfaces.Fig. 3Safe design of MOx by surface passivation.…”
BackgroundThe wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties.ResultsTHP-1 and BEAS-2B cells were exposed to 0–200 μg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx.ConclusionsThe surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0193-5) contains supplementary material, which is available to authorized users.
“…The tetrahedral phosphonic groups in this complex limit the free space around the central metal atoms, which are shielded from interacting with ligands in biological environment such as protons, biomolecules, etc . Since EDTMP was reported to have strong binding affinity with heavy metal ions [30–32], this coating may be used for a broad spectrum of toxic MOx to provide stable inert surfaces.Fig. 3Safe design of MOx by surface passivation.…”
BackgroundThe wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties.ResultsTHP-1 and BEAS-2B cells were exposed to 0–200 μg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx.ConclusionsThe surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0193-5) contains supplementary material, which is available to authorized users.
“…In the case of a rigid dimer, at least three different P resonances should occur in the spectra: (i) the P atoms of the two CH 2 PO 3 2Ϫ arms at the coordinating side of the molecule, (ii) the coordinated P of the partially bound side of the molecule, and (iii) the P of the non-coordinating CH 2 PO 3 2Ϫ arm of this side. On the other hand, in the case of a flexible dimer the methylene protons in the N-attached phosphonate arms should become equivalent resulting in the appearance of a high-intensity doublet in the 1 H NMR spectra, which is not observed, instead rather complicated spectra are obtained (see Figure 4) were suggested by Westerback et al [7] and by Motekaitis et al, [10] and partly confirmed by Jarvis et al [11] [22,24] The pK a calculated from the data in Table 3 for the deprotonation of [AlLH] 4Ϫ to produce [AlL] 5Ϫ is 6.26, significantly lower than the pK a of the free ligand with the same number of protons, HL (pK a ഠ 13; see Table 2). This considerable decrease in the pK a of the HL 7Ϫ proton due to the coordination of Al III indicates the high stability of the hexadentate coordinated complex [AlL] 5Ϫ .…”
Section: Complexesmentioning
confidence: 86%
“…Sm III and Ho III by Jarvis et al [11] ) because of the use of EDTMPϪlanthanide complexes as therapeutic radiopharmaceuticals. Fe III ϪEDTMP complexes have been investigated by Westerback et al, [7] Motekaitis et al [9] and Oakes et al, [14] but only in a qualitative way, with no reports of any definite data. In a recent paper, Popov et al [15] reported a critical evaluation of the proton-and metal-complexation stability constants to be found in the literature up to 2000 for various aminophosphonic acids.…”
The complexation properties (including stoichiometries and stability constants of the complexes formed) of ethylenediaminetetramethylenephosphonic acid with Al III and V IV O were studied in aqueous solution at an ionic strength of 0.2 M KCl, at 25°C by means of pH potentiometry. For Al III both mononuclear (AlLH n ) and dinuclear (Al 2 LH n ) species were found in solution, whereas for V IV O only mononuclear complexes were detected. For each metal ion, a solid
“…We can safely say that the phosphate group might be as effective or even more effective than the carboxylate group in contributing to the chelating tendencies of polyfunctional acid [5]. These differences mainly stem from the strong pH dependence on the complex formation, added bulkiness, and bidentate coordination ability of the phosphonate group, as well as their potential for formation of polymecric species.…”
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