Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells
Abstract
:1. Introduction
2. Results
2.1. GNP Cellular Distribution
2.2. Absorption in Nuclear Membrane
2.3. Inter-Cellular Effects and Cell Membrane Absorption
3. Discussion
3.1. GNP Cellular Distribution
3.2. Absorption in Nuclear Membrane
3.3. Inter-Cellular Effects and Cell Membrane Absorption
3.4. Validation and Limitations
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
GNP | Gold Nanoparticle |
EPR | Enhanced Permeation and Retention |
LEM | Local Effect Model |
WNP | Water Nanoparticle |
LET | Linear Energy Transfer |
References
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Simulation | Dose Per Proton (eV) (GNP) | Yield Per Proton (GNP) | DEF | REF | Main Results | |||||
---|---|---|---|---|---|---|---|---|---|---|
N | C | N | C | N | C | N | C | |||
Cluster size (nm) | 100 | 5.30 | 63.6 | 0.537 | 5.66 | 1.07 | 1.17 | 1.08 | 1.17 | 200 nm clusters had yields 117% and 25% greater than for 500 nm clusters for nucleus and cytoplasm respectively |
200 | 4.63 | 64.1 | 0.459 | 5.73 | 1.07 | 1.15 | 1.10 | 1.14 | ||
500 | 2.17 | 50.7 | 0.212 | 4.59 | 1.16 | 1.19 | 1.17 | 1.19 | ||
Cluster distribution | Near nucleus | 4.63 | 64.1 | 0.459 | 5.73 | 1.07 | 1.15 | 1.10 | 1.14 | Clusters near nucleus increased nucleus yield by 91% while reducing cytoplasm yield by 7% compared to a disperse distribution |
Whole Cytoplasm | 2.47 | 68.4 | 0.240 | 6.15 | 1.09 | 1.18 | 1.12 | 1.17 | ||
Number of Clusters | 500 | 2.49 | 32.3 | 0.246 | 2.88 | 1.15 | 1.17 | 1.16 | 1.17 | Dose and yield per GNP changed by less than 7% indicating a good scaling with GNP concentration |
1000 | 4.63 | 64.1 | 0.459 | 5.73 | 1.07 | 1.15 | 1.10 | 1.14 | ||
2000 | 9.21 | 126.5 | 0.913 | 11.3 | 1.13 | 1.16 | 1.14 | 1.16 |
Simulation | Cluster Diameter (nm) | Total Number of GNPs (104) | Distribution Range from Nucleus (nm) | Nuclear Membrane Permeability (%) | Cell Membrane Permeability (%) | Proton Energy (MeV) |
---|---|---|---|---|---|---|
Effect of cluster distribution | 200 | 10 | 1000, 2250 | 100 | 100 | 5 |
Effect of Cluster size | 100, 200, 500 | 10 | 1000 | 100 | 100 | 5 |
Effect of GNP concentration | 200 | 5, 10, 20 | 1000 | 100 | 100 | 5 |
Nuclear membrane absorption | 200 | 10 | 1000 | 0 | 100 | 5 |
Effect in adjacent cell | 200 | 10 | 1000 | 100 | 100 | 5 |
Cell membrane absorption | 200 | 10 | 1000 | 100 | 0 | 5 |
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Peukert, D.; Kempson, I.; Douglass, M.; Bezak, E. Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells. Int. J. Mol. Sci. 2020, 21, 4431. https://doi.org/10.3390/ijms21124431
Peukert D, Kempson I, Douglass M, Bezak E. Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells. International Journal of Molecular Sciences. 2020; 21(12):4431. https://doi.org/10.3390/ijms21124431
Chicago/Turabian StylePeukert, Dylan, Ivan Kempson, Michael Douglass, and Eva Bezak. 2020. "Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells" International Journal of Molecular Sciences 21, no. 12: 4431. https://doi.org/10.3390/ijms21124431