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Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses.

Pan CH, Liu WT, Bien MY, Lin IC, Hsiao TC, Ma CM, Lai CH, Chen MC, Chuang KJ, Chuang HC - Int J Nanomedicine (2014)

Bottom Line: The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs.The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences.This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Institute of Labor, Occupational Safety and Health, Ministry of Labor, Taipei Medical University Hospital, Taipei, Taiwan ; School of Public Health, National Defense Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.

ABSTRACT
Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFβ signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.

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Alterations in average hydrodynamic diameters, zeta potentials, pH values, and zinc concentrations in supernatants when 20–500 μg/mL ZnONP20, ZnONP90, or Al-ZnONP20 was suspended in 10% FBS solution for 48 hours. Asterisks indicate significant differences compared with control at P<0.05.Abbreviations: ZnONP, zinc oxide nanoparticle; FBS, fetal bovine serum.
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f2-ijn-9-3631: Alterations in average hydrodynamic diameters, zeta potentials, pH values, and zinc concentrations in supernatants when 20–500 μg/mL ZnONP20, ZnONP90, or Al-ZnONP20 was suspended in 10% FBS solution for 48 hours. Asterisks indicate significant differences compared with control at P<0.05.Abbreviations: ZnONP, zinc oxide nanoparticle; FBS, fetal bovine serum.

Mentions: To understand the physicochemical characteristics of the ZnONPs, we next investigated the hydrodynamic diameters of ZnONP20, ZnONP90, and Al-ZnONP20 at 20–500 μg/mL in 10% FBS-containing medium over 48 hours. The results of this analysis, as shown in Figure 2, indicate that the hydrodynamic diameters of the ZnONPs were 105 (at 20 μg/mL) to 522 (at 500 μg/mL) nm for ZnONP20, 98 (at 20 μg/mL) to 486 (at 500 μg/mL) nm for ZnONP90, and 53 (at 20 μg/mL) to 967 (at 500 μg/mL) nm for Al-ZnONP20 for 48 hours. The hydrodynamic diameters of the ZnONPs increased over time, especially after 24-hour exposure (P<0.05, except for ZnONP20 and ZnONP90 at 20 μg/mL). The zeta potentials of the ZnONPs were determined, as shown in Figure 2. The zeta potentials of ZnONP20, ZnONP90, and Al-ZnONP20 were between −17.56 and −29.56 mV, −26.51 and −34.99 mV, and −21.62 and −29.25, respectively, compared with −18.17 mV for 10% FBS (vehicle control, 0 μg/mL). The absolute value of zeta-potential values increased over time during the 48-hour period (P<0.05), except for ZnONP20 at 150 and 300 μg/mL. A slight increase in pH values was observed when these particles were dispersed in the FBS solution (Figure 2, P<0.05), except for ZnONP90 at 150 μg/mL. We observed that the pH values were 8.03–8.24 for ZnONP20, 7.92–8.16 for ZnONP90, and 7.92–8.32 for Al-ZnONP20. Zn leaching from these particles during the 48-hour period was also investigated. We observed that the concentrations of Zn that leached from ZnONP20 significantly increased over time (P<0.05) and also demonstrated a significant dose-dependent response (P<0.05), as shown in Figure 2. The concentrations of Zn that leached from ZnONP90 and Al-ZnONP20 increased to a peak at 0.5 hour and remained stable throughout the remaining incubation time.


Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses.

Pan CH, Liu WT, Bien MY, Lin IC, Hsiao TC, Ma CM, Lai CH, Chen MC, Chuang KJ, Chuang HC - Int J Nanomedicine (2014)

Alterations in average hydrodynamic diameters, zeta potentials, pH values, and zinc concentrations in supernatants when 20–500 μg/mL ZnONP20, ZnONP90, or Al-ZnONP20 was suspended in 10% FBS solution for 48 hours. Asterisks indicate significant differences compared with control at P<0.05.Abbreviations: ZnONP, zinc oxide nanoparticle; FBS, fetal bovine serum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128792&req=5

f2-ijn-9-3631: Alterations in average hydrodynamic diameters, zeta potentials, pH values, and zinc concentrations in supernatants when 20–500 μg/mL ZnONP20, ZnONP90, or Al-ZnONP20 was suspended in 10% FBS solution for 48 hours. Asterisks indicate significant differences compared with control at P<0.05.Abbreviations: ZnONP, zinc oxide nanoparticle; FBS, fetal bovine serum.
Mentions: To understand the physicochemical characteristics of the ZnONPs, we next investigated the hydrodynamic diameters of ZnONP20, ZnONP90, and Al-ZnONP20 at 20–500 μg/mL in 10% FBS-containing medium over 48 hours. The results of this analysis, as shown in Figure 2, indicate that the hydrodynamic diameters of the ZnONPs were 105 (at 20 μg/mL) to 522 (at 500 μg/mL) nm for ZnONP20, 98 (at 20 μg/mL) to 486 (at 500 μg/mL) nm for ZnONP90, and 53 (at 20 μg/mL) to 967 (at 500 μg/mL) nm for Al-ZnONP20 for 48 hours. The hydrodynamic diameters of the ZnONPs increased over time, especially after 24-hour exposure (P<0.05, except for ZnONP20 and ZnONP90 at 20 μg/mL). The zeta potentials of the ZnONPs were determined, as shown in Figure 2. The zeta potentials of ZnONP20, ZnONP90, and Al-ZnONP20 were between −17.56 and −29.56 mV, −26.51 and −34.99 mV, and −21.62 and −29.25, respectively, compared with −18.17 mV for 10% FBS (vehicle control, 0 μg/mL). The absolute value of zeta-potential values increased over time during the 48-hour period (P<0.05), except for ZnONP20 at 150 and 300 μg/mL. A slight increase in pH values was observed when these particles were dispersed in the FBS solution (Figure 2, P<0.05), except for ZnONP90 at 150 μg/mL. We observed that the pH values were 8.03–8.24 for ZnONP20, 7.92–8.16 for ZnONP90, and 7.92–8.32 for Al-ZnONP20. Zn leaching from these particles during the 48-hour period was also investigated. We observed that the concentrations of Zn that leached from ZnONP20 significantly increased over time (P<0.05) and also demonstrated a significant dose-dependent response (P<0.05), as shown in Figure 2. The concentrations of Zn that leached from ZnONP90 and Al-ZnONP20 increased to a peak at 0.5 hour and remained stable throughout the remaining incubation time.

Bottom Line: The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs.The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences.This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Institute of Labor, Occupational Safety and Health, Ministry of Labor, Taipei Medical University Hospital, Taipei, Taiwan ; School of Public Health, National Defense Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.

ABSTRACT
Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFβ signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.

Show MeSH
Related in: MedlinePlus