ISSN 1028-3358, Doklady Physics, 2018, Vol. 63, No. 3, pp. 96–99. © Pleiades Publishing, Ltd., 2018. Original Russian Text © A.V. Belousov, V.N. Morozov, G.A. Krusanov, M.A. Kolyvanova, A.P. Chernyaev, A.A. Shtil, 2018, published in Doklady Akademii Nauk, 2018, Vol. 479, No. 2, pp. 137–140.
PHYSICS
Modeling the Effect of Surface Modification of Gold Nanoparticles Irradiated with 60Co on the Secondary Рarticles Emission Spectrum A. V. Belousova, V. N. Morozova, b,*, G. A. Krusanovc, M. A. Kolyvanovab, A. P. Chernyaeva, c, and A. A. Shtild Presented by Academician L.A. Il’in September 25, 2017 Received September 25, 2017
Abstract—The Monte Carlo method (computer simulation) is used to construct a physical model of secondary particles emission induced by the simulated irradiation of a gold nanoparticle with 60Co. It is demonstrated that the modification of the nanoparticle surface with polyethylene glycol affects the spectrum of secondary electrons produced in a nanoparticle and leaving it and its shell. The model takes into account the size and the chemical composition of the shell and provides an opportunity to design antitumor radiosensitizers based on gold nanoparticles. DOI: 10.1134/S1028335818030059
Progress in fundamental research into the mechanisms of the biological action of ionizing radiation and the introduction of more advanced instrumentation have contributed to a considerable enhancement of radiotherapy efficiency. However, the issue of augmenting the radiation-induced damage to tumor cells and reducing the radiation dose absorbed by nontumor tissues still stands. The general approach to enhancing the efficiency of radiation therapy (effected through tumor oxygenation, local hyperthermia, or hyperglycemia) consists in increasing the amount of cytotoxic metabolites produced in tumor cells and their immediate environment as a result of irradiation. This mechanism forms the basis of a promising treatment method: the use of nanomaterials containing elements with high atomic numbers as chemical dose modifiers.
energy into the kinetic energy of charged particles, thus increasing the number of secondary electrons and free radicals produced in the process of radiolysis of water. The efficiency of nanoparticles acting as radiosensitizers depends on the type and the energy of ionizing radiation; the material, the size, the shape, and the surface structure of nanoparticles; and their concentration and localization in a cell [1, 2]. These parameters need to be adjusted for specific clinical settings. Gold nanoparticles are characterized by a high (relative to tissues) mass attenuation coefficient, chemical inertness in physiological conditions, and biocompatibility. Their shape and size may vary within a wide range; in addition, such particles offer ample opportunities for surface functionalization and conjugation of various ligands (low-molecular-weight compounds, peptides, antibodies, etc.) for directional delivery of nanoparticles to a tumor and aggregation prevention in high-ionic-strength media (blood plasma) [3].
Elements with high atomic numbers have large cross sections of interaction with photons and facilitate the conversion of electromagnetic radiation
Polyethylene glycol (PEG) is often used for nanoparticle surface modification. The radiosensitizing action of gold nanoparticles with PEG shells with various molecular weights has been demonstrated experimentally [4–6]. However, the influence of such a shell on the radiosensitizing efficiency remains understudied. The magnitude of the radiosensitizing effect depends on the shell thickness [7]; when the PEG shell becomes thicker, the yield of free radicals decreases [8]. The latter parameter is proportional to
a Department
of Physics, Moscow State University, Moscow, 119991 Russia b Burnazyan Federal Medical Biophysical Center, Moscow, 123182 Russia c Skobeltsyn Institute of Nuclear Physics, Moscow State University, Moscow, 119991 Russia d Blokhin National Medical Oncology Research Center, Moscow, 115478 Russia *e-mail:
[email protected] 96
MODELING THE EFFECT OF SURFACE MODIFICATION
17 nm 8.5 nm
Photons 60 nm
Au PEG
Fig. 1. Nanoparticle model for Monte Carlo calculations.
the energy of the particles (mostly electrons) leaving the shell; their spatial distribution is defined by the energy spectrum of the particles. In the general case, the shell of a nanoparticle alters the spectral composition of the secondary emission. Thus, modification of the nanoparticle surface induces changes in both the spatial distribution of free radicals produced in the process of radiolysis of water and their overall number. The aim of the present study is to model the effect of a PEG shell on the spectrum of secondary emission of a gold nanoparticle subjected to gamma-irradiation. The Geant4 code was used for Monte Carlo modeling. The radiation source was a circular (60 nm in diameter) beam of photons with energies of 1.17 and 1.33 MeV (a total of 64 × 109 primary photons), which corresponds
97
to the emission of 60Co. These photons were incident on gold nanoparticles with a diameter of 17 nm. Nanoparticles without a shell (model 1) and with a PEG shell (model 2) were used in the first and the second series of tests, respectively (Fig. 1). The PEG layer thickness was set to 8.5 nm [9]. This value is close to 6.5 nm, which is the size of a PEG macromolecule with a molecular weight of 5000 g/mol calculated using the random coil model (the size of this PEG molecule in the plane zigzag model is 38 nm). The shell was assumed to be homogeneous and to have the following elemental composition by mass: 38.71% C, 9.68% H, and 51.61% O. End thiol groups, which bind PEG molecules chemically to the nanoparticle surface, were neglected. Secondary electrons are produced in a gold nanoparticle subjected to gamma-irradiation. These electrons leave the nanoparticle and ionize water. The number of secondary electrons leaving the nanoparticle was calculated in model 1. In model 2, the number of electrons leaving the particle and the PEG shell was also determined, with the addition that electrons produced in the particle itself were distinguished from particles produced in the shell. The results of computer simulation revealed differences between the models in the number of emitted secondary particles (Table 1) and in their energy spectrum. Figure 2 shows the energy spectra of photons and electrons produced in each model under gammairradiation. The spectral distributions of photons leaving the gold nanoparticle in model 1 and the shell in model 2 have no statistically significant differences (Fig. 2a). Figure 2b presents the energy spectra of secondary electrons. Considerable differences between
Table 1. Numerical parameters of the energy spectra of secondary particles Type of secondary radiation
Number
Mean energy, MeV Total energy, MeV
Photons leaving the gold nanoparticle
1868 ± 43
(4.7 ± 0.1) × 10–2
88 ± 2
2049 ± 45
–2
97 ± 2
Photons leaving the PEG shell Electrons leaving the gold nanoparticle
In sum:
–2
5744 ± 71
–2
4205 ± 56
(37.2 ± 0.3) × 10
compton
10275 ± 101
ionization
1812 ± 42
photoeffect
3342 ± 58
with an energy below 2 keV
5293 ± 73
In sum:
17288 ± 132
–2
(44.4 ± 0.3) × 10
7675 ± 81
compton
13092 ± 114
(46.0 ± 0.3) × 10–2
6020 ± 68
ionization
883 ± 30
(1.9 ± 0.2) × 10–4
0.170 ± 0.015
photoeffect
3313 ± 58
(46.2 ± 0.1) × 10–2
1537 ± 42
with an energy below 2 keV
4010 ± 63
(9.4 ± 0.1) × 10–4
produced in the shell
4740 ± 69
(46.3 ± 0.6) × 10–2
2198 ± 41
produced in the nanoparticle
12548 ± 112
(43.7 ± 0.4) × 10–2
5478 ± 69
Electrons leaving the PEG shell
DOKLADY PHYSICS
15429 ± 124
(4.7 ± 0.1) × 10
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(40.9 ± 0.4) × 10
(1.45 ± 0.01) × 10 (46.1 ± 0.1) × 10 (7.7 ± 0.1) × 10
–4
–2
–4
0.263 ± 0.013 1539 ± 42 4.100 ± 0.075
3.768 ± 0.071
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BELOUSOV et al.
the low-energy spectral components in models 1 and 2 are seen clearly. At the same time, the differences in the high-energy region (above 1 MeV) of the spectrum of secondary electrons are within the measurement accuracy. Owing to the fact that the free-path length of photons is large, cellular damage and radiosensitization are induced primarily by secondary electrons. Since the molecule ionization threshold is 1−10 eV, lowenergy electrons, which differ considerably in number in models 1 and 2, may be essential to this process. The authors of [10] have identified three regions around a nanoparticle with a specific type of secondary electrons prevalent in each region. The free-path length of electrons sets the size of these regions. The free-path length of secondary electrons in water varies from several nanometers for low-energy electrons (
