Limits...
Nanodiamonds act as Trojan horse for intracellular delivery of metal ions to trigger cytotoxicity.

Zhu Y, Zhang Y, Shi G, Yang J, Zhang J, Li W, Li A, Tai R, Fang H, Fan C, Huang Q - Part Fibre Toxicol (2015)

Bottom Line: In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values.Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity.The present experimental and theoretical results provide useful insight into understanding of cytotoxicity triggered by nanoparticle-ion interactions, and open new ways in the interpretation of nanotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Division of Physical Biology, and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China. zhuying@sinap.ac.cn.

ABSTRACT

Background: Nanomaterials hold great promise for applications in the delivery of various molecules with poor cell penetration, yet its potential for delivery of metal ions is rarely considered. Particularly, there is limited insight about the cytotoxicity triggered by nanoparticle-ion interactions. Oxidative stress is one of the major toxicological mechanisms for nanomaterials, and we propose that it may also contribute to nanoparticle-ion complexes induced cytotoxicity.

Methods: To explore the potential of nanodiamonds (NDs) as vehicles for metal ion delivery, we used a broad range of experimental techniques that aimed at getting a comprehensive assessment of cell responses after exposure of NDs, metal ions, or ND-ion mixture: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Trypan blue exclusion text, optical microscope observation, synchrotron-based scanning transmission X-ray microscopy (STXM) and micro X-ray fluorescence (μXRF) microscopy, inductively coupled plasma-mass spectrometry (ICP-MS), reactive oxygen species (ROS) assay and transmission electron microscopy (TEM) observation. In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values.

Results: The adsorption capacity of NDs for different metal ions was different, and the adsorption for Cu2+ was the most strong among divalent metal ions. These different ND-ion complexes then had different cytotoxicity by influencing the subsequent cellular responses. Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity. By theoretical approaches, we demonstrated that the functional carbon surface and cluster structures of NDs made them good vehicles for metal ions delivery.

Conclusions: NDs played the Trojan horse role by allowing large amounts of metal ions accumulate into living cells followed by subsequent release of ions in the interior of cells, which then led to cytotoxicity. The present experimental and theoretical results provide useful insight into understanding of cytotoxicity triggered by nanoparticle-ion interactions, and open new ways in the interpretation of nanotoxicity.

No MeSH data available.


Related in: MedlinePlus

Cu2+vectorized by NDs induced more remarkable cytotoxicity than by other nanoparticles. Trypan blue exclusion test of cell viability after incubation with various kinds of nanoparticle-Cu2+ mixture for 24 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4374301&req=5

Fig2: Cu2+vectorized by NDs induced more remarkable cytotoxicity than by other nanoparticles. Trypan blue exclusion test of cell viability after incubation with various kinds of nanoparticle-Cu2+ mixture for 24 h.

Mentions: Since the delivery of Cu2+ by NDs leads to most obvious cellular responses, a detailed investigation of the interaction between NDs and Cu2+ is performed in the following experiment. From the kinetics curves and adsorption isotherm curves, we can see that large amounts of Cu2+ were adsorbed very rapidly by NDs, and saturation was achieved in less than 30 min (see Additional file 1: Figure S4). Optical microscopy (Figure 1d) images show that NDs were remarkably internalized and existed as dark granules in the cytoplasm. Addition of NDs improved the Cu2+ induced morphology changes and significantly reduced the cell number. Trypan blue exclusion test shows that addition of NDs decreased the cell viability from 52% to 12%, while cell survival of NDs alone was 96%. We also examined the cell viability of other nanoparticle-Cu2+ mixture by typan blue exclusion test. Results show that cellular responses are more remarkable when Cu2+ was vectorized by NDs than by ultra-small graphene oxide (sGO) or nanocarbon blacks (CBs) with similar size (Figure 2 and Additional file 1: Figure S5, S6), indicating that the unique geometries of ND clusters play an important role. NDs dispersed in aqueous solution can spontaneously form clusters with a lower free energy [33]. In our previous work [19], a model for the spatial configuration of ND clusters has been proposed. According to this model, it is speculated that metal ions can rapidly and freely diffuse along the nano-scaled pores of the ND cluster, leading to a relatively high adsorption capability.Figure 2


Nanodiamonds act as Trojan horse for intracellular delivery of metal ions to trigger cytotoxicity.

Zhu Y, Zhang Y, Shi G, Yang J, Zhang J, Li W, Li A, Tai R, Fang H, Fan C, Huang Q - Part Fibre Toxicol (2015)

Cu2+vectorized by NDs induced more remarkable cytotoxicity than by other nanoparticles. Trypan blue exclusion test of cell viability after incubation with various kinds of nanoparticle-Cu2+ mixture for 24 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374301&req=5

Fig2: Cu2+vectorized by NDs induced more remarkable cytotoxicity than by other nanoparticles. Trypan blue exclusion test of cell viability after incubation with various kinds of nanoparticle-Cu2+ mixture for 24 h.
Mentions: Since the delivery of Cu2+ by NDs leads to most obvious cellular responses, a detailed investigation of the interaction between NDs and Cu2+ is performed in the following experiment. From the kinetics curves and adsorption isotherm curves, we can see that large amounts of Cu2+ were adsorbed very rapidly by NDs, and saturation was achieved in less than 30 min (see Additional file 1: Figure S4). Optical microscopy (Figure 1d) images show that NDs were remarkably internalized and existed as dark granules in the cytoplasm. Addition of NDs improved the Cu2+ induced morphology changes and significantly reduced the cell number. Trypan blue exclusion test shows that addition of NDs decreased the cell viability from 52% to 12%, while cell survival of NDs alone was 96%. We also examined the cell viability of other nanoparticle-Cu2+ mixture by typan blue exclusion test. Results show that cellular responses are more remarkable when Cu2+ was vectorized by NDs than by ultra-small graphene oxide (sGO) or nanocarbon blacks (CBs) with similar size (Figure 2 and Additional file 1: Figure S5, S6), indicating that the unique geometries of ND clusters play an important role. NDs dispersed in aqueous solution can spontaneously form clusters with a lower free energy [33]. In our previous work [19], a model for the spatial configuration of ND clusters has been proposed. According to this model, it is speculated that metal ions can rapidly and freely diffuse along the nano-scaled pores of the ND cluster, leading to a relatively high adsorption capability.Figure 2

Bottom Line: In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values.Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity.The present experimental and theoretical results provide useful insight into understanding of cytotoxicity triggered by nanoparticle-ion interactions, and open new ways in the interpretation of nanotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Division of Physical Biology, and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China. zhuying@sinap.ac.cn.

ABSTRACT

Background: Nanomaterials hold great promise for applications in the delivery of various molecules with poor cell penetration, yet its potential for delivery of metal ions is rarely considered. Particularly, there is limited insight about the cytotoxicity triggered by nanoparticle-ion interactions. Oxidative stress is one of the major toxicological mechanisms for nanomaterials, and we propose that it may also contribute to nanoparticle-ion complexes induced cytotoxicity.

Methods: To explore the potential of nanodiamonds (NDs) as vehicles for metal ion delivery, we used a broad range of experimental techniques that aimed at getting a comprehensive assessment of cell responses after exposure of NDs, metal ions, or ND-ion mixture: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Trypan blue exclusion text, optical microscope observation, synchrotron-based scanning transmission X-ray microscopy (STXM) and micro X-ray fluorescence (μXRF) microscopy, inductively coupled plasma-mass spectrometry (ICP-MS), reactive oxygen species (ROS) assay and transmission electron microscopy (TEM) observation. In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values.

Results: The adsorption capacity of NDs for different metal ions was different, and the adsorption for Cu2+ was the most strong among divalent metal ions. These different ND-ion complexes then had different cytotoxicity by influencing the subsequent cellular responses. Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity. By theoretical approaches, we demonstrated that the functional carbon surface and cluster structures of NDs made them good vehicles for metal ions delivery.

Conclusions: NDs played the Trojan horse role by allowing large amounts of metal ions accumulate into living cells followed by subsequent release of ions in the interior of cells, which then led to cytotoxicity. The present experimental and theoretical results provide useful insight into understanding of cytotoxicity triggered by nanoparticle-ion interactions, and open new ways in the interpretation of nanotoxicity.

No MeSH data available.


Related in: MedlinePlus