Intracellular Biotransformation of Ultrasmall Iron Oxide Nanoparticles and Their Effect in Cultured Human Cells and in Drosophila Larvae In Vivo
Abstract
:1. Introduction
2. Results and Discussion
2.1. Cellular Uptake and Intracellular Dissolution of Ultra-Small FeAT-NPs
2.2. Biological Effects
2.2.1. Cell Viability and Clonogenic Activity
2.2.2. ROS Induction
2.2.3. In Vitro DNA Damage: Comet Assay
2.2.4. In Vivo Somatic Mutation and Recombination: SMART Assay
3. Materials and Methods
3.1. Instrumentation
3.2. Chemicals and Materials
3.3. Synthesis of Ultrasmall Iron Hydroxide Adipate Tartrate Nanoparticles
3.4. Cell Lines, Cell Culture and Drosophila Strains
3.5. Quantification of Iron in Cells and D. melanogaster Larvae, and Iron Speciation
3.6. Cell Viability Assay
3.7. Clonogenic Activity
3.8. Reactive Oxygen Species Measurement
3.9. Comet Assay
3.10. In Vivo SMART Assay of Drosophila
3.11. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Value |
---|---|
RF Power [W] | 1550 |
Coolant gas flow [L min−1] | 14.0 |
Auxiliary gas flow [L min−1] | 0.8 |
Carrier gas flow [L min−1] | 0.8 |
Measurement mode | Single Quadrupole |
Cell gas flow [mL min−1] | 0.31(H2) |
Q1 bias [V] | 0 |
Qcell bias [V] | −5.94 |
Q3 bias [V] | −12.0 |
Q1 masses [u] | Open |
Q3 masses [u] | 56 (56Fe+) |
Number of spots | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Repair | Conc. | Scored | Small | Medium | Large | Total | Spot | Clones/ | |||||
Status | Sex a | (mM) b | Eyes | N | % | N | % | N | % | N | % | Size c | 104 Cells |
NER+ | F | 0 | 734 | 61 | 8.31 | 6 | 0.82 | 0 | 0.00 | 67 | 9.13 | 2.14 | 4.88 |
0.5 | 392 | 34 | 8.67 | 3 | 0.77 i | 2 | 0.51 i | 39 | 9.95 | 2.49 | 6.19 | ||
1 | 416 | 35 | 8.41 | 8 | 1.92 i | 0 | 0.00 i | 43 | 10.34 | 2.19 | 5.66 | ||
1.5 | 412 | 33 | 8.01 | 14 | 3.40+ | 1 | 0.24 i | 48 | 11.65 | 2.5 | 7.28 | ||
2 | 580 | 70 | 12.07+ | 12 | 2.07 i | 2 | 0.34 i | 84 | 14.48 + | 2.34 | 8.47 | ||
5 | 510 | 53 | 10.39 | 15 | 2.94 + | 3 | 0.59 i | 71 | 13.92 + | 2.65 | 9.22 | ||
MMS | 402 | 81 | 20.15+ | 46 | 11.44 + | 16 | 3.98 + | 143 | 35.57 + | 4.04 | 34.67 | ||
M | 0 | 752 | 28 | 3.72 | 5 | 0.66 | 0 | 0.00 | 33 | 4.39 | 2.16 | 2.37 | |
0.5 | 400 | 14 | 3.50 | 1 | 0.25 i | 0 | 0.00 i | 15 | 3.75 | 2.06 | 1.93 | ||
1 | 412 | 19 | 4.61 i | 1 | 0.24 i | 0 | 0.00 i | 20 | 4.85 | 2.05 | 2.49 | ||
1.5 | 430 | 17 | 3.95 i | 6 | 1.40 i | 0 | 0.00 i | 23 | 5.35 i | 2.26 | 3.02 | ||
2 | 542 | 41 | 7.56 + | 7 | 1.29 i | 0 | 0.00 i | 48 | 8.86 + | 2.06 | 4.56 | ||
5 | 508 | 35 | 6.89 + | 10 | 1.97 i | 0 | 0.00 i | 45 | 8.86 + | 2.36 | 5.23 | ||
MMS | 392 | 46 | 11.73 + | 19 | 4.85 + | 4 | 1.02 + | 69 | 17.60 + | 3.25 | 14.30 | ||
NER− | F | 0 | 610 | 56 | 9.18 | 12 | 1.97 | 1 | 0.16 | 69 | 11.31 | 2.30 | 3.26 |
0.1 | 316 | 35 | 11.08 | 5 | 1.58 i | 3 | 0.95 i | 43 | 13.61 | 3.30 | 5.62 | ||
0.25 | 308 | 31 | 10.06 | 6 | 1.95 i | 2 | 0.65 i | 39 | 12.66 | 3.21 | 5.07 | ||
0.5 | 492 | 61 | 12.40 | 10 | 2.03 i | 1 | 0.20 i | 72 | 14.63 | 2.27 | 4.09 | ||
1 | 310 | 33 | 10.65 | 10 | 3.23 i | 0 | 0.00 i | 43 | 13.87 | 2.28 | 3.95 | ||
2.5 | 298 | 30 | 10.07 | 8 | 2.68 i | 3 | 1.01 i | 41 | 13.76 | 4.05 | 6.96 | ||
5 | 304 | 27 | 8.88 | 9 | 2.96 i | 0 | 0.00 i | 36 | 11.84 | 2.33 | 3.45 | ||
MMS | 410 | 102 | 24.88 | 62 | 15.12 + | 45 | 10.98 + | 209 | 50.98 + | 5.25 | 33.48 | ||
M | 0 | 510 | 32 | 6.27 | 5 | 0.98 | 1 | 0.20 | 38 | 7.45 | 2.38 | 2.28 | |
0.1 | 302 | 15 | 4.97 | 1 | 0.33 i | 1 | 0.33 i | 17 | 5.63 | 2.41 | 1.70 | ||
0.25 | 302 | 19 | 6.29 | 2 | 0.66 i | 0 | 0.00 i | 21 | 6.95 | 2.19 | 1.90 | ||
0.5 | 494 | 33 | 6.68 | 6 | 1.21 i | 0 | 0.00 i | 39 | 7.89 | 2.13 | 2.10 | ||
1 | 280 | 16 | 5.71 | 5 | 1.79 i | 1 | 0.36 i | 22 | 7.86 | 3.05 | 2.99 | ||
2.5 | 282 | 17 | 6.03 | 0 | 0.00 i | 1 | 0.35 i | 18 | 6.38 | 2.89 | 2.31 | ||
5 | 306 | 18 | 5.88 | 2 | 0.65 i | 0 | 0.00 i | 20 | 6.54 | 2.10 | 1.72 | ||
MMS | 406 | 56 | 13.79 + | 29 | 7.14 + | 7 | 1.72 + | 92 | 22.66 + | 3.19 | 9.05 |
Number of spots | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Repair | Conc. | Scored | Small | Medium | Large | Total | Spot | Clones/ | |||||
Status | Sex a | (mM) b | Eyes | N | % | N | % | N | % | N | % | Size c | 104 Cells |
NER+ | F | 0 | 682 | 67 | 8.57 | 9 | 1.15 | 0 | 0.00 | 76 | 9.72 | 2.15 | 5.28 |
0.1 | 512 | 39 | 7.62 | 9 | 1.76 i | 1 | 0.20 i | 49 | 9.57 | 2.45 | 5.86 | ||
0.25 | 350 | 27 | 7.71 | 6 | 1.71 i | 1 | 0.29 i | 34 | 9.71 | 2.97 | 7.85 | ||
0.5 | 428 | 33 | 7.71 | 11 | 2.57 i | 1 | 0.23 i | 45 | 10.51 | 2.76 | 7.25 | ||
1 | 542 | 52 | 9.59 | 8 | 1.48 i | 2 | 0.37 i | 62 | 11.44 | 2.38 | 6.81 | ||
2 | 208 | 33 | 10.71 | 4 | 1.30 i | 0 | 0.00 i | 37 | 12.01 | 2.32 | 6.97 | ||
MMS | 534 | 103 | 16.25 + | 42 | 6.62 + | 17 | 2.68 + | 162 | 25.55 + | 3.97 | 24.53 | ||
M | 0 | 592 | 31 | 4.48 | 2 | 0.29 | 0 | 0.00 | 33 | 4.77 | 2.11 | 2.49 | |
0.1 | 442 | 18 | 4.07 | 2 | 0.45 i | 0 | 0.00 i | 20 | 4.52 | 2.19 | 2.35 | ||
0.25 | 310 | 16 | 5.16 i | 1 | 0.32 i | 0 | 0.00 i | 17 | 5.48 i | 2.06 | 2.99 | ||
0.5 | 352 | 15 | 4.26 | 5 | 1.42 i | 0 | 0.00 i | 20 | 5.68 i | 2.45 | 3.48 | ||
1 | 508 | 27 | 5.31 i | 1 | 0.20 i | 0 | 0.00 i | 28 | 5.51 | 2.04 | 2.81 | ||
2 | 208 | 14 | 4.52 | 2 | 0.65 i | 0 | 0.00 i | 16 | 5.16 | 2.09 | 2.76 | ||
MMS | 502 | 49 | 8.14 + | 18 | 2.99 + | 2 | 0.33 i | 69 | 11.46 + | 2.53 | 6.80 | ||
NER− | F | 0 | 302 | 30 | 9.93 | 6 | 1.99 | 0 | 0.00 | 36 | 11.92 | 2.19 | 3.27 |
0.1 | 308 | 30 | 9.74 | 5 | 1.62 i | 3 | 0.97 i | 38 | 12.34 | 3.21 | 4.95 | ||
0.25 | 302 | 30 | 9.93 | 4 | 1.32 i | 1 | 0.33 i | 35 | 11.59 | 2.40 | 3.48 | ||
0.5 | 304 | 31 | 10.20 | 6 | 1.97 i | 2 | 0.66 i | 39 | 12.83 | 3.97 | 6.37 | ||
1 | 304 | 32 | 10.53 | 3 | 0.99 i | 0 | 0.00 i | 35 | 11.51 | 2.11 | 3.04 | ||
MMS | 308 | 68 | 22.08 + | 37 | 12.01 + | 12 | 3.90 + | 117 | 37.99 + | 4.55 | 21.61 | ||
0 | 300 | 18 | 6.00 | 2 | 0.67 | 0 | 0.00 | 20 | 6.67 | 2.10 | 1.75 | ||
0.1 | 306 | 18 | 5.88 | 1 | 0.33 i | 0 | 0.00 i | 19 | 6.21 | 2.06 | 1.59 | ||
M | 0.25 | 304 | 22 | 7.24 i | 1 | 0.33 i | 0 | 0.00 i | 23 | 7.57 i | 2.04 | 1.93 | |
0.5 | 304 | 19 | 6.25 i | 4 | 1.32 i | 0 | 0.00 i | 23 | 7.57 i | 2.19 | 2.07 | ||
1 | 302 | 23 | 7.62 i | 2 | 0.66 i | 0 | 0.00 i | 25 | 8.28 i | 2.12 | 2.19 | ||
MMS | 300 | 43 | 14.33 + | 15 | 5.00 + | 3 | 1.00 i | 61 | 20.33 + | 3.08 | 7.84 |
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Rodríguez Pescador, A.; Gutiérrez Romero, L.; Blanco-González, E.; Montes-Bayón, M.; Sierra, L.M. Intracellular Biotransformation of Ultrasmall Iron Oxide Nanoparticles and Their Effect in Cultured Human Cells and in Drosophila Larvae In Vivo. Int. J. Mol. Sci. 2022, 23, 8788. https://doi.org/10.3390/ijms23158788
Rodríguez Pescador A, Gutiérrez Romero L, Blanco-González E, Montes-Bayón M, Sierra LM. Intracellular Biotransformation of Ultrasmall Iron Oxide Nanoparticles and Their Effect in Cultured Human Cells and in Drosophila Larvae In Vivo. International Journal of Molecular Sciences. 2022; 23(15):8788. https://doi.org/10.3390/ijms23158788
Chicago/Turabian StyleRodríguez Pescador, Alonso, Lucía Gutiérrez Romero, Elisa Blanco-González, María Montes-Bayón, and L. María Sierra. 2022. "Intracellular Biotransformation of Ultrasmall Iron Oxide Nanoparticles and Their Effect in Cultured Human Cells and in Drosophila Larvae In Vivo" International Journal of Molecular Sciences 23, no. 15: 8788. https://doi.org/10.3390/ijms23158788