A Monte Carlo Program Package for Predicting Physical Enhancement from Nanomaterials Under X-Ray Irradiation

Appendix A A Monte Carlo Program Package for Predicting Physical Enhancement from Nanomaterials Under X-Ray Irradiation

Introduction

This appendix describes a theoretical modeling package developed by the Guo group at UC Davis. The package uses a Monte Carlo method to calculate physical enhancement by nanomaterials under X-ray irradiation. A Matlab version was created and published in 2007 by Guo et al. [1], and the Mathematica package was ﬁrst published in 2012 by Guo et al. [2]. The current package uses the Geant4 code to calculate electron emission from atoms in nanomaterials upon X-ray absorption and the NOREC code to calculate energy deposition in water by electrons. Shapes of nanomaterials are created in a number of C++ programs, and visualization and implementation are done in homemade Mathematica programs. The whole package is called LLSG, using the initial letters of the last names of the authors who helped develop the package (Lee-Lu-Sharmah-Guo). As shown in Chap. 2, there are several ways to model physical enhancement. The fundamental physical principles to model physical enhancement by nanomaterials under X-ray irradiation are similar to those of atoms and the bulk, which have been successfully developed over the last century. The main difference between modeling nanomaterials and other materials is that the shape of nanostructures needs to be considered. These shapes modify the energy spectrum of electrons released from the nanomaterials under X-ray irradiation. Many packages are now available to calculate physical enhancement, although some are more user-friendly than others. A brief summary of these packages is given in Sect. 2.3.3. As stated above, Guo et al. [1–3] developed the Monte Carlo-based simulation package to calculate enhancement generated from different nanostructures when irradiated by ionizing radiation such as X-rays. Prior to the work published in 2012, calculations performed in the Guo group, with all the physical processes considered, were done with homemade programs similar to that of PENELOPE [4]. In the 2012 publication, the atomic processes were replaced with Geant4 v. 9.6, and energy deposition in water was performed using NOREC. The remaining homemade part

© Springer International Publishing AG, part of Springer Nature 2018 465 T. Guo, X-ray Nanochemistry, Nanostructure Science and Technology, https://doi.org/10.1007/978-3-319-78004-7 466 Appendix A A Monte Carlo Program Package... was transformed from the Matlab code to the C++ code that created the shapes of nanomaterials from which electrons were emitted as a result of interactions between X-rays and nanomaterials. Mathematica was chosen for its features of visualization and implementation. The combined program is the LLSG package. The main contribution of LLSG is the use of nanomaterials of various shapes and compositions. Geant4 and other similar packages have basic shape features to predict physical enhancement of nanostructures. However, they are often not ade- quate to model complicated nanostructures demanded by X-ray nanochemistry research. It is important to point out that many of the existing modeling calculations predict only energy deposition enhancement. They, including the LLSG package shown here, do not calculate the amounts of reactive oxygen species or other properties such as DNA damage or hydroxylation or polymerization reactions using the quantum chemistry methods. There are several packages such as Geant4-DNA or PARTRAC that have incorporated some chemical or biochemical features are brieﬂy reviewed in Chap. 2, although neither package includes actual molecular (quantum) simulations to model actual biochemical reactions.

Description of the Simulation Method

The package developed by Guo et al. [2] calculates physical enhancement by nanostructures of different shapes, compositions, and assemblies. The central parts of the simulation are X-ray absorption by nanomaterials, electron emission from nanomaterials, electron transport, and energy deposition in both water and nanomaterials. Monte Carlo approach is used to follow each X-ray photon and then electron. The enhancement is defined as the ratio of energy deposition in water with nanomaterials to without nanomaterials, which gives relative enhancement. Relative enhancement is then subtracted by 1 to obtain absolute enhancement. In this simulation package, enhancement factor is the numerical value of the dose incurred in water with nanomaterials when irradiated with the flux of X-rays that deposit 1 Gy of X-rays in pure water. The units of enhancement are dose enhancement units (DEU). Energy loss of electrons in nanomaterials is modeled after the Bethe formula [5], which does not produce more electrons as electrons traverse in materials but simply reduces the energy of the electrons of interest as they traverse the nanomaterials. If transport does not occur in the volume of interest such as in type 1 or 2 physical enhancement regions, then the deposition is not recorded. This means energy deposition events in nanomaterials are not recorded. If the deposition occurs in water, then the amount of energy deposition is recorded for enhancement determination. Figure A.1 shows the overall flowchart. The Monte Carlo method, which has built-in Geant4 and NOREC, is interfaced with the homemade C++ program along with the nanomaterial shape features as a code in Mathematica and is linked to the C Appendix A A Monte Carlo Program Package... 467

Fig. A.1 Overall ﬂowchart. The simulation begins at X-ray absorption and creation of electrons. These electrons are then traverse nanomaterials and water. Energy deposited in water is recorded. Shapes of nanomaterials are embedded in the program. The number of electrons used in the simulation is speciﬁed at the beginning. Each electron is followed until its energy is below 7.4 eV. Enhancement value is then computed using the normalized energy deposited in water volume of interest 468 Appendix A A Monte Carlo Program Package...

++ program. An executable file is then built. All implementation and visualization is carried out in Mathematica by calling the C++ generated executable. Figure A.2 shows the production of electrons from nanomaterials upon X-ray absorption. Two processes are investigated. The first is photoelectron emission. This is handled by the code G4CrossSectionHandler/EPDL97. Once a vacancy is created, the filling of the vacancy is simulated using the Geant4 G4AtomicDeexcitation/ EADL code, which examines all the vacancies until they are pushed to the continuum. Figure A.3 shows the flowchart for electron transport in the medium such as water. The flowchart shows the routine that is used to perform the electron transport

e– Emission

Photoe– Auger e–

Begin Auger Cascade Submit E γ (G4AtomicDeexcitation: EADL)

Decide a shell of Ebind to ionize (G4CrossSectionHandler : Decide a shell to move 1st vacancy to EPDL97) Decide energy release path Pop/push the old/new vacancy

Push Vacancy – Auger no Push e with Eγ – E bind ? yes

Decide a shell to release e– from Push the emitted e– Push the new vacancy

no All Vacancies in Continuum? yes Begin Next Iteration

Fig. A.2 Flowchart of the algorithm that tracks the relaxation history of electrons emitted from X-ray absorbing atoms with a distribution of photoelectrons carrying different energies resulting from absorption of an X-ray photon (of energy Eγ) by an atom. Low-energy electromagnetic package from Geant4 Collaboration (G4CrossSectionHandler and G4AtomicDeexciation) available online from CERN is employed in the simulation. (Adopted from Guo et al. [2]. Copyright (2012) American Chemical Society) Appendix A A Monte Carlo Program Package... 469

Fig. A.3 Flowchart of the algorithm that tracks the transport of electrons in Au or other nanomaterials and in water. A geometry is defined first, which is given in the Mathematica program. Then a number of electrons are emitted from a randomly selected gold atom in the gold nanostructure. These electrons then traverse through the nanostructure and then water until their energy is lower than 7.4 eV. Bethe formula is used to calculate energy loss in the gold nanostructure or nanostructures of other compositions, and NOREC is used to calculate energy loss in water. (Adopted from Guo et al. [2]. Copyright (2012) American Chemical Society) simulation. This routine is repeated with a fixed geometry and at different initial electron energies Ee to obtain the average energy deposition. The initial electron is placed in a chosen starting material (e.g., Au) at a random position and direction. The electron then enters the electron queue, and the transport begins. The NIST Electron Inelastic-Mean-Free-Path Database and Electron Elastic-Scattering Cross-Section Database are used in the simulation of transport in Au, and the energy 470 Appendix A A Monte Carlo Program Package... lost in each step Δl is computed using a continuous energy loss formula. Once the electron moves out of Au and reaches water, NOREC is used to simulate the transport of both primary and secondary electrons in water. These electrons are tested for boundary crossing, and the electrons that enter a material (e.g., Au) are again placed in the electron queue with the positions (xi, yi, zi) and the energy Ei (i represents the ith electron) at the time of crossing. The electrons are transported individually until the electron queue is empty. Each electron is removed from the queue when the energy goes below Emin (7.4 eV) either in water or in other materials.

Algorithm

The program integrates Geant4 modules, NIST database, and NOREC with homemade codes in C++ and Mathematica to calculate X-ray absorption, electron generation, electron transport, and electron energy loss in nanomaterials and water with different types and shapes of material. The compiled C++ programs and header ﬁles are placed in folders together with the required codes from Geant4 and NOREC as well as the homemade Monte Carlo code that includes geometrical shapes. In the following subsections, steps taken to build the executable are described. The proce- dure is shown as follows.

Building the Modules

Assembling the Program Components

The first part is to add Geant4 modules into the homemade Monte Carlo program written in C++. Geant4 source file and the related data files can be downloaded from the official Geant4 website (http://geant4.cern.ch/). The Geant4 modules G4CrossSectionHandler (EPDL97) and G4AtomicDeexcitation (EADL) are incorporated into the homemade Monte Carlo program to account for ionization of the photoelectron electron and the subsequent auger cascade, respectively. The second part is to incorporate NOREC module into the homemade Monte Carlo program to simulate event-by-event history of a primary electron along with all its secondary particles in liquid water as they traverse through liquid water until a threshold energy of 7.4 eV is reached. The third part is to write a C++ program for generating different geometric shapes of nanomaterials. The program is then compiled to generate an executable file, which is called “nano.” The simulation can be run and visualized using Mathematica program after installing the C++ program generated executable. A separate Mathematica routine, named varShapes, is written to call the geometric shapes written in C++. The entire program with all the source files, data files, C++ program, and the Mathematica routine for calling C++ written geometric shapes are saved in one directory called NANO. Appendix A A Monte Carlo Program Package... 471

Initialization

When running the simulation in Mathematica, ﬁrst set the directory to where the program and related ﬁles are stored:

SetDirectory[“C:\\Users\\usrn\Desktop\NANO”]

Then call the Mathematica routine for geometric shapes:

Get[“varShapes.m”]

The command ?varShapes`* lists the geometric shapes (and related command) that can be used for simulation. The list of shapes included in calculation is listed below.

To run the simulation for enhancement calculation, install the Monte Carlo code executable generated in C++:

Install[“nano.exe”]

Generic Variables

Three variables are important to the calculation. The ﬁrst is “ntrj” which is the number of electrons emitted from atoms in the added nanomaterials. The convergence of calculations depends on this number—the greater the number, the more convergence the calculation. However, the calculating time is also proportional to the number. If time allows, it is recommended to have the maximum number of electrons emitted from the atoms so that the calculation satisfactorily converges. The second variable is “xray,” which is the energy of X-rays. It is monochromatic. 472 Appendix A A Monte Carlo Program Package...

If a spectrum of X-rays is desired, then the enhancement at each X-ray energy has to be computed, and the results are combined to produce the result. The X-ray flux of any desired X-ray energy is automatically chosen to deposit a uniform dose of 1 Gy in water. The flux is then normalized using the number of absorptions (trajectories). The term trajectory is used here, although it means the number of electrons emitted after X-ray absorption. In many calculations, 1000 electrons are used to obtain converging results. Two routines are critical. The first is the routine “GetEDDx,” which is used to calculate the energy deposition density (unit: eV cmÀ3 GyÀ1) in water at different distances from the origin. The second routine “GetEnh” is used to calculate the enhancement. Theoretically, the enhancement should be calculated as a ratio of energy deposition density using GetEDDx at locations due to a nanoparticle in water to the energy deposited in water due to water alone obtained. In practice, energy deposition in water in the presence of nanomaterials in Gy is the enhancement because the flux of X-rays is normalized to 1 Gy of X-ray-induced energy deposition in pure water.

Description of Enhancement Calculation

Below is the representative description of how an enhancement calculation is performed for a gold nanoparticle in water inside a given box.

Energy Deposition in presence of NanomaterialðÞ EDD Relative Enhancement ¼ Energy Deposition by Water Alone ðA:1Þ

Whereas,

Energy Deposition in presence of NanomaterialðÞ EDD Absolute Enhancement ¼ À 1 Energy Deposition by Water Alone ðA:2Þ

Stepwise breakdown of general enhancement calculation for unit dose is described below: • Compute X-ray ﬂux per Gy of dose and energy deposited per unit dose in water. • Obtain energy deposition due to nanomaterial (EDDx) in the unit of eV/nm3:

– Set material type (Au, Ag, SiO2, etc.), shape, size in nm, geometry, X-ray energy in keV, box size, periodic boundary condition, number of electrons for simulation. – Compute volume of box in nm3, volume of material in nm3, and delete water volume equal to material volume. Appendix A A Monte Carlo Program Package... 473

– Obtain tables for electron absorption cross-section (g/ cm2) table, electron emission spectrum, and electron emission probability for “x” keV photon for the material. – Compute and tabulate EDDe (energy deposition for each electron). – Count and sum absorption and emission probability-weighted energy deposition due to all electrons (EDDX). • Compute relative enhancement ¼ EDDx/energy deposited per unit dose in water. For X-ray doses other than the unit dose, energy deposition is linearly scaled for both water and the material prior to computing relative enhancement.

Examples of Calculations Calculating Physical Enhancement in Mathematica

Some of the calculation details are shown below, which can further explain how LLSG works.

Type 2 Physical Enhancement (T2PE) from Nanomaterials

For a nanomaterial that produces enhancement under X-ray irradiation, it is possible to predict either the type 1 or 2 physical enhancement. The calculation is set in a box, ﬁlled with water and desired nanostructures as shown in Fig. A.4. This box is like a unit cell in a crystal. A periodic boundary condition ﬂag (PB) is used to specify whether the unit is a stand-alone box or if there are other boxes around it. When PB ¼ 1, as shown in Fig. A.4, the calculation results include contribution from neighboring boxes, which means electrons leaving the box will return and reenter the

Stopped Tracking Continue to Track electron electron

PB=0 PB=1

Fig. A.4 Explanation of the periodic boundary condition in enhancement calculations. When PB ¼ 0, electrons leaving the box will not be tracked and therefore are considered to be terminated in the calculation. When PB ¼ 1, the electron left in the box will be sent to the opposite, as if the electron never left the box, until the energy of the electron is lower than 7.4 eV 474 Appendix A A Monte Carlo Program Package... box as speciﬁed by the periodic condition until the electron energy falls below 7.4 eV. When PB ¼ 0, the calculation is on a single nanostructure in a water cube/ box, and electrons leaving the box do not return. As a result, when PB ¼ 0, there should be no type 1 physical enhancement. For a single spherical solid gold nanoparticle, the command to perform the calculation is:

Calculation Name = GetEnh[GetEDDx[{“Material Symbol”}, {Material radius.}, X-ray Energy in keV, ntrj, Box Size., PB]]

The output generated can be plotted using Mathematica commands. For simplic- ity the output for each calculation here is shown after a speciﬁed calculation code is given. If type 2 physical enhancement (T2PE) (i.e., PB ¼ 0) due to a 100 nm diameter gold nanoparticle under irradiation by 40 keV X-rays is to be calculated, the command for enhancement calculation for a box size of 1000 nm (box size can be used to control or specify the nanoparticle concentration) and using 1000 trajectories is:

Au50T2 = GetEnh[GetEDDx[{“Au”}, {50.}, 40, 1000, 1000., 0]]

The results can be plotted in Mathematica using command:

ListPlot[Au50T2, PlotRange -> {{x1,x2}, {y1, y2}}, Frame -> True, Joined -> True, FrameLabel -> {“x-label”, “y-label”}

T2 (100 nm AuNP)

4 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm)

The data can also be exported as a text file using command shown below and will save the data file in “desktop” as a text file with a file name Au50T2.dat. Appendix A A Monte Carlo Program Package... 475

Export["C:\\Users\\PC-Name\\Desktop\\Au50T2.dat", Au50T2]

If one wants to calculate T2PE due to silver nanoparticle, then one has to use the “Ag” as the material symbol. For example:

Ag50T2 = GetEnh[GetEDDx[{“Ag”}, {50.}, 40, 1000, 1000., 0]]

T2 (100 nm AgNP) 8

4 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm)

For a spherical shell of gold and with water inside and outside the shell, the command line looks like this:

AuShell50T2=GetEnh[GetEDDx[{“H2O”, “Au”}, {50., 10.}, 40, 1000, 1000., 0]]

T2 (120 nm Au Nanoshell of 10 nm thick shell)

10 Enhancement 5

0 0 100 200 300 400 500 Distance from origin (nm) 476 Appendix A A Monte Carlo Program Package...

To calculate T2PE for silver nanoshell, it is sufﬁcient to use “Ag” as material symbol, as shown below:

Agshell50T2 = GetEnh[GetEDDx[{"H2O", "Ag"}, {50., 10.}, 40, 1000, 1000., 0]]

T2 (120 nm Ag Nanoshell of 10 nm thick shell)

6 Enhancement 4

0 0 100 200 300 400 500 Distance from origin (nm)

The data can either be plotted or exported as text ﬁle using similar command as shown for a gold particle above. The speciﬁed command indicates that the shell thickness is 10 nm, whereas the inner radius is 50 nm, thus representing a gold spherical shell of 120 nm in diameter. The inner radius is represented by water indicating that the nanostructure is a hollow gold shell with water interior of 100 nm diameter and outer gold layer of 10 nm thickness.

Type 1 Physical Enhancement from Nanomaterials

The type 1 physical enhancement (T1PE) is calculated by setting the periodic boundary condition ﬂag PB to 1. For example, to determine T1PE (i.e., PB ¼ 1) due to a 100 nm diameter gold nanoparticle under irradiation by 40 keV X-rays, the command for enhancement calculation for a box size of 1000 nm and using 1000 trajectories is:

Au50T1 = GetEnh[GetEDDx[{“Au”}, {50.}, 40, 1000, 1000., 1]] Appendix A A Monte Carlo Program Package... 477

T1 (100 nm AuNP)

Enhancement 4

0 0 100 200 300 400 500 Distance from origin (nm)

It is worth pointing out that enhancement far away from the gold nanoparticle is no longer zero. Similarly, T1PE for 120 nm Au nanoshell with 10 nm thick shell can be calculated as:

Aushell50T1 = GetEnh[GetEDDx[{"H2O", "Au"}, {50., 10.}, 40, 1000, 1000., 1]]

T1 (120 nm Au Nanoshell of 10 nm thick shell) 20

10 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm)

A brief list of representative calculations as implemented in Mathematica is listed in Appendix B. 478 Appendix A A Monte Carlo Program Package...

Contacts

Those who are interested in getting a copy of LLSG package can send an email request to [email protected]. A downloading website may be created if the demand is strong. The package is free of charge with proper attribution.

References

1. Carter, J. D., Cheng, N. N., Qu, Y. Q., Suarez, G. D., & Guo, T. (2007). Nanoscale energy deposition by x-ray absorbing nanostructures. The Journal of Physical Chemistry. B, 111, 11622–11625. 2. Lee, C., Cheng, N. N., Davidson, R. A., & Guo, T. (2012). Geometry enhancement of nanoscale energy deposition by X-rays. Journal of Physical Chemistry C, 116, 11292–11297. 3. Sharmah, A., Yao, Z., Lu, L., & Guo, T. (2016). X-ray-induced energy transfer between nanomaterials under X-ray irradiation. Journal of Physical Chemistry C, 120, 3054–3060. 4. Salvat, F., Fernandez-Varea, J. M., & Sempau, J. (2011). PENELOPE-2011: A code system for Monte Carlo simulation of electron and photon transport. Spain: Nuclear Energy Agency. 5. Joy, D., & Luo, S. (1989). An empirical stopping power relationship for low-energy electrons. Scanning, 11, 176–180. Appendix B Sample Calculations of LLSG

These are the actual examples obtained by running the Mathematica program. Therefore, no ﬁgure captions are given. Comments are given within the Mathematica program. Plots are generated after the commands are executed.

SetDirectory["C:\\Users\\Guo Lab\\Desktop\\NANO"] C:\Users\Guo Lab\Desktop\NANO Get["varShapes.m"] Install["nano.exe"]

(*T2 Enhancement for 100 nm Au particle*)

Au50T2=GetEnh[GetEDDx[{"Au"},{50.},40,1000,1000.,0]]; ListPlot[Au50T2,PlotRange->{{0,500},Full},Frame->True, PlotLabel-> "T2 (100 nm AuNP)",Joined->True,FrameLabel->{"Distance from origin (nm)","Enhancement"}]

© Springer International Publishing AG, part of Springer Nature 2018 479 T. Guo, X-ray Nanochemistry, Nanostructure Science and Technology, https://doi.org/10.1007/978-3-319-78004-7 480 Appendix B Sample Calculations of LLSG

T2 (100 nm AuNP)

4 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm)

(*T1 Enhancement for 100 nm Au particle*)

Au50T1=GetEnh[GetEDDx[{"Au"},{50.},40,1000,1000.,1]]; ListPlot[Au50T1,PlotRange->{{0,500},Full},Frame->True, PlotLabel-> "T1 (100 nm AuNP)",Joined->True,FrameLabel->{"Distance from origin (nm)","Enhancement"}]

T1 (100 nm AuNP)

Enhancement 4

0 0 100 200 300 400 500 Distance from origin (nm) Appendix B Sample Calculations of LLSG 481

(*T2 Enhancement for 120 nm spherical Au shell with 10 nm thick shell and 100 nm inner diameter*)

Aushell50T2=GetEnh[GetEDDx[{"H2O","Au"},{50., 10.},40,1000,1000.,0]]; ListPlot[Aushell50T2,PlotRange->{{0,500},Full},Frame->True, PlotLabel-> "T2 (120 nm Au Nanoshell of 10 nm thick shell)",Joined- >True,FrameLabel->{"Distance from origin (nm)","Enhancement"}]

T2 (120 nm Au Nanoshell of 10 nm thick shell)

10 Enhancement 5

0 0 100 200 300 400 500 Distance from origin (nm)

(* T1 Enhancement for 120 nm spherical Au shell with 10 nm thick shell and 100 nm inner diameter*)

Aushell50T1=GetEnh[GetEDDx[{"H2O","Au"},{50., 10.},40,1000,1000.,1]]; ListPlot[Aushell50T1,PlotRange->{{0,500},Full},Frame->True, PlotLabel-> "T1 (120 nm Au Nanoshell of 10 nm thick shell)",Joined- >True,FrameLabel->{"Distance from origin (nm)","Enhancement"}] 482 Appendix B Sample Calculations of LLSG

T1 (120 nm Au Nanoshell of 10 nm thick shell) 20

10 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm)

(*T2 Enhancement for 100 nm Ag particle*)

Ag50T2=GetEnh[GetEDDx[{"Ag"},{50.},40,1000,1000.,0]]; ListPlot[Ag50T2,PlotRange->{{0,500},Full},Frame->True, PlotStyle-> {Black, Dashed, Thick},PlotLabel-> "T2 (100 nm AgNP)", Joined->True,FrameLabel->{"Distance from origin (nm)","Enhancement"}]

T2 (100 nm AgNP) 8

4 Enhancement

0 0 100 200 300 400 500 Distance from origin (nm) Appendix B Sample Calculations of LLSG 483

(* T1 Enhancement for 120 nm spherical Au shell with 10 nm thick shell and 100 nm inner diameter*)

Agshell50T2=GetEnh[GetEDDx[{"H2O","Ag"},{50., 10.},40,1000,1000.,0]]; ListPlot[Agshell50T2,PlotRange->{{0,500},Full},Frame->True, PlotStyle-> {Black, Dashed, Thick},PlotLabel-> "T2 (120 nm Ag Nanoshell of 10 nm thick shell)",Joined->True,FrameLabel-> {"Distance from origin (nm)","Enhancement"}]

T2 (120 nm Ag Nanoshell of 10 nm thick shell)

6 Enhancement 4

0 0 100 200 300 400 500 Distance from origin (nm)

(*A calcium phosphate shell (CaP) satellite and a AuNP*) r=50.0;d=10.0;R=50.0;xray=40;ntrj=1000;distRange=Range [0.0,100.0,10.0];GraphicsRow[Table[DrawSatellite[r,d,R,L],{L, distRange}]]

ergDepFromShell=GetErgSatellite["CaP","Shell",R,0.,r,d,xray,3. *2*(r+d+2*R),ntrj] 0.540282 ergDepFromBall=Table[GetErgSatellite["Au","Ball",R,dist,r,d, xray,3.*2*(r+d+dist+2*R),ntrj],{dist,distRange}] {4.06113,3.6051,2.26051,1.98854,2.127,1.50759,1.30803, 1.12849,0.922778,0.792548,0.834466} EnhFromShell=(ergDepFromShell/(4π/3 (r^3)))//GetEnh 0.165363 AllShellEnh={EnhFromShell,EnhFromShell,EnhFromShell, EnhFromShell,EnhFromShell,EnhFromShell,EnhFromShell, EnhFromShell,EnhFromShell,EnhFromShell,EnhFromShell} 484 Appendix B Sample Calculations of LLSG

{0.165363,0.165363,0.165363,0.165363,0.165363,0.165363, 0.165363,0.165363,0.165363,0.165363,0.165363} EnhFromBall=(ergDepFromBall/(4π/3 (r^3)))//GetEnh {1.24298,1.1034,0.691867,0.608628,0.651006,0.461423,0.400344, 0.345392,0.282432,0.242573,0.255403} EnhFromTotal=((ergDepFromBall+ergDepFromShell)/(4π/3 (r^3)))// GetEnh {1.40834,1.26877,0.85723,0.773991,0.816368,0.626786,0.565707, 0.510755,0.447795,0.407936,0.420765} ticks=Table[i,{i,0,100,10}];ListPlot[{Transpose[{ticks, AllShellEnh}],Transpose[{ticks,EnhFromBall}],Transpose[{ticks, EnhFromTotal}]},PlotRange->All,Joined->True,Frame->True, FrameLabel->{"Distance from origin (nm)","Enhancement"}, PlotLegends->{"Shell","Ball (AuNP)","Total"}]

1.4 Shell Ball (AuNP) 1.2 Total

1.0

0.8

0.6 Enhancement 0.4

0.2

0.0 0 20 40 60 80 100 Distance from origin (nm)

(*A calcium phosphate shell (CaP) satellite and multiple AuNPs*) r=50.0;d=10.0;R=50.0;xray=40;range={1,3,6};GraphicsRow[Table [DrawFlower[r,d,R,n],{n,range}]]

L=1.0;ergDepFromBall=GetErgFlower["Au","Ball",R,L,r,d,xray,3. *2*(r+d+2*R),ntrj] 4.06113 ergDepFromShell=GetErgFlower["CaP","Shell",R,L,r,d,xray,3.*2*(r +d+2*R),ntrj] Appendix B Sample Calculations of LLSG 485

0.540282 Enh33Shell=(ergDepFromShell/(4π/3 (r^3)))//GetEnh 0.165363 Enh33Shell=((ergDepFromBall+ergDepFromShell)/(4π/3 (r^3)))// GetEnh 1.40834 Enh33Shelln3=((3*ergDepFromBall+ergDepFromShell)/(4π/3 (r^3)))// GetEnh 3.8943 Enh33Shelln6=((6*ergDepFromBall+ergDepFromShell)/(4π/3 (r^3)))// GetEnh 7.62323

(*For multiple gold nanoparticles on silica shells such that total mass of gold remains same*)

gparamHedron={50.,10.};xray=40;simbox=1000.;ntrj=1000; OneHedronEnh=(GetErgOne["Au",gparamHedron,xray,simbox,ntrj]/ GetVinOne[gparamHedron])//GetEnh 1.52038

TwoHedronEnh=(GetErgTwo["Au",gparamHedron,xray,simbox,ntrj]/ GetVinTwo[gparamHedron])//GetEnh 2.56535

ThreeHedronEnh=(GetErgThree["Au",gparamHedron,xray,simbox, ntrj]/GetVinThree[gparamHedron])//GetEnh 2.93275

FourHedronEnh=(GetErgFour["Au",gparamHedron,xray,simbox,ntrj]/ GetVinFour[gparamHedron])//GetEnh 3.35691

FiveHedronEnh=(GetErgFive["Au",gparamHedron,xray,simbox,ntrj]/ GetVinFive[gparamHedron])//GetEnh 3.74449

SixHedronEnh=(GetErgSix["Au",gparamHedron,xray,simbox,ntrj]/ GetVinSix[gparamHedron])//GetEnh 3.89291

IcosaHedronEnh=(GetErgIcosa["Au",gparamHedron,xray,simbox, ntrj]/GetVinIcosa[gparamHedron])//GetEnh 5.27155

DodecaHedronEnh=(GetErgDodeca["Au",gparamHedron,xray,simbox, ntrj]/GetVinDodeca[gparamHedron])//GetEnh 6.79264

PentakisHedronEnh=(GetErgPentakis["Au",gparamHedron,xray, simbox,ntrj]/GetVinPentakis[gparamHedron])//GetEnh 8.46715 486 Appendix B Sample Calculations of LLSG

shellHedronEnh=(GetErgShell["Au",gparamHedron,xray,simbox, ntrj]/GetVinShell[gparamHedron])//GetEnh 16.7901

test1=Grid[{ {"Shape","Enhancement","Parameters"}, {DrawOne[gparamHedron],OneHedronEnh, Grid[{{"radius VOI =",50}, {"radius ball =",GettOne[50,10]},{"x-ray =",xray}}]},{DrawTwo [gparamHedron],TwoHedronEnh, Grid[{{"radius VOI =",50},{"radius ball =",GettTwo[50,10]},{"x-ray =",xray}}]},{DrawThree [gparamHedron],ThreeHedronEnh, Grid[{{"radius VOI =",50}, {"radius ball =",GettThree[50,10]},{"x-ray =",xray}}]},{DrawFour [gparamHedron],FourHedronEnh, Grid[{{"radius VOI =",50},{"radius ball =",GettFour[50,10]},{"x-ray =",xray}}]},{DrawFive [gparamHedron],FiveHedronEnh, Grid[{{"radius VOI =",50},{"radius ball =",GettFive[50,10]},{"x-ray =",xray}}]},{DrawSix [gparamHedron],SixHedronEnh, Grid[{{"radius VOI =",50},{"radius ball =",GettSix[50,10]},{"x-ray =",xray}}]},{DrawIcosa [gparamHedron],IcosaHedronEnh, Grid[{{"radius VOI =",50}, {"radius ball =",GettIcosa[50,10]},{"x-ray =",xray}}]}, {DrawDodeca[gparamHedron],DodecaHedronEnh,Grid[{{"radius VOI=",50},{"radius ball =",GettDodeca[50,10]},{"x-ray =", xray}}]}, {DrawPentakis[gparamHedron],PentakisHedronEnh,Grid[{{"radius VOI=",50},{"radius ball =",GettPentakis[50,10]},{"x-ray =", xray}}]}, {DrawShellHedron[gparamHedron],shellHedronEnh,Grid[{{"radius shell=",50},{"thickness =",10},{"x-ray =",xray}}]}},Frame->All] Appendix B Sample Calculations of LLSG 487

Shape Enhancement Parameters

radius VOI = 50 1.52038 radius ball = 44.9794 x-ray = 40

radius VOI = 50 2.56535 radius ball = 35.7002 x-ray = 40

radius VOI = 50 2.93275 radius ball = 31.187 x-ray = 40

radius VOI = 50 3.35691 radius ball = 28.3353 x-ray = 40

radius VOI = 50 3.74449 radius ball = 26.3041 x-ray = 40 488 Appendix B Sample Calculations of LLSG

Shape Enhancement Parameters

radius VOI = 50 3.89291 radius ball = 24.7531 x-ray = 40

radius VOI = 50 5.27155 radius ball = 19.6466 x-ray = 40

radius VOI = 50 6.79264 radius ball = 16.5706 x-ray = 40

radius VOI = 50 8.46715 radius ball = 14.1676 x-ray = 40

radius shell = 50 16.7901 thickness = 10 x-ray = 40 Appendix B Sample Calculations of LLSG 489

(*For enhancement within region bound by two sheet-like arrays of gold nanoparticles*)

Lplate=200.;hplate=5.;ndivide=5.;DrawPlateT[{Lplate,hplate, ndivide}]

GetErgPlateT["Au",{Lplate,hplate,ndivide},40.,1.5*Max [Lplate,12.+hplate],100]/GetVinPlateT[{Lplate,hplate, ndivide}]//GetEnh 9.07521

(*Calculation and visualition of electron tracks for gold nanoshell*)

(*for Xray = 15 keV*)

rsh=50.0;dsh=10.0;xray=15;dose=50.;BSize=500.;shellTrj=GetTrjx [{"H2O","Au"},{rsh,dsh},xray,dose,"TRJ","",10*2*(rsh+dsh),0]; AuShellTrj=PlotTrj[shellTrj,rsh,dsh,1/1 BSize] 490 Appendix B Sample Calculations of LLSG

Show[%121,Axes->True] Appendix B Sample Calculations of LLSG 491

500

–500 500

–500 –500

500

(∗for Xray = 40 keV∗)

(*for Xray = 40 keV*)

rsh=50.0;dsh=10.0;xray=40;dose=50.;BSize=500.;shellTrj=GetTrjx [{"H2O","Au"},{rsh,dsh},xray,dose,"TRJ","",10*2*(rsh+dsh),0]; AuShellTrj=PlotTrj[shellTrj,rsh,dsh,1/1 BSize] 492 Appendix B Sample Calculations of LLSG

Show[%97,Axes->True] Appendix B Sample Calculations of LLSG 493

500

–500 500

–500 –500

500

(∗for Xray = 81 keV∗)

(*for Xray = 81 keV*)

rsh=50.0;dsh=10.0;xray=81;dose=50.;BSize=500.;shellTrj=GetTrjx [{"H2O","Au"},{rsh,dsh},xray,dose,"TRJ","",10*2*(rsh+dsh),0]; AuShellTrj=PlotTrj[shellTrj,rsh,dsh,1/1 BSize] 494 Appendix B Sample Calculations of LLSG

Show[%124,Axes->True] Appendix B Sample Calculations of LLSG 495

500

–500 500

–500 –500

500

End Index

A Anti-enhancement Absolute enhancement, 12, 13 definition, 121 Absolute physical enhancement, 46 DNA strands Acceptors, 97 hydroxyl radical cleavage, 194 A549 cells, 370 SSB, 194 Addition algorithm, enhancements gold-chitosan nanocomposites, 183 chemical probes, 185 gold nanotubes, 150, 194 physical, 184 ligands, 149 T1PE and T2PE PEG ligands, 193 AuNPs and CaPELs, 186, 187 physical enhancement, 177 large nanoparticles, 185, 186 ROS, 123 nanoscale probe, 186 subtraction algorithm, 195 probing chemical species, 185 TMA ligands, 150, 193 relative and absolute enhancements, X-ray irradiation, 183 188, 189 Apoptosis-resistant cancer cells, 380 XIET, 186 Arc radiation therapy, 384 volume fraction, 185 Arginine-glycine-aspartic acid (RGD) Advance Photon Sources (APS), 316 peptides, 376 Aggregated nanoparticles, 220 Atomic absorption (AA) spectroscopy, 305, 361 AGuIX®, 357 ATP production, 161 Amine-terminated fifth-generation Au@MnO2-PEG, 384, 385 dendrimers, 317 Auger cascading processes, 30 Amino-phenyl-fluorescein (APF), 118, 142, 244 Auger electrons, 29–31, 55, 58, 62, 94, 95, 334 Angular anisotropy, 41 anisotropy, 31 Animal models, 240, 241 emission anisotropy, 41 Animal work, medical applications therapy, 7, 17 biodistribution, 312 Auger processes, 29, 30, 380 enhancement measurements and Auger therapy, 299 calculations, 313 Average energy deposition density, 89 irradiation protocols, 313 mice/rats, 311 nanoparticle delivery/tracking, 311 B targeting, 311–312 Bacteria, 170–172 tumor sizes/life span changes, 310 BEAMnrc code, 61, 332 Anisotropic angular distribution, 30 Beer’s law, 28

3-Benzoic acid, 244, 245 C Bethe formula, 34, 62 C++, 465, 466, 470, 471 Biodistribution Calcium phosphate, 211 nanomaterials in animals, 312 Calcium phosphate-enclosed liposomes surfactants, 327–329 (CaPELs), 56, 81, 98, 181, Biological enhancement, 12, 25, 159, 161, 183, 211, 212, 229 196, 462 Calcium phosphate shell (CaP), 484 anti-enhancement, 160 Calculated energy deposition, 94 carbohydrates, 285 Calibrations, 70 in bacteria, 170–172 Canadian National Research Council (NRC), 52 CCS, 172 Cancer and animal treatment cell division cycle, 173 array of parallel microbeams of X-rays, 332 cellular characteristics, 173 BEAMnrc/DOSXYZnrc code, 332 chemical, 160 calculated electrons tracks in water, 334, 335 complex cellular systems, 162 capillary phantoms, 335, 336 deﬁnition, 159 cellular structures, 337 DEU, 159 DER, 337 DNA repairs, 160 DNA strand break enhancement factor, 336 dose hypofractionation, 173 dose enhancement calculations, 337 in eukaryotic cells, 166–169 energy deposition, 332, 334, 337, 338 factors, 160 homogeneous and inhomogeneous identiﬁcation, 161 distribution, 337 magnitude, 161 in vitro measurements, 337 nanomaterials, 173 (see also Nanomaterials) MCNP-5, 334 outcome, 160 Monte Carlo packages, 336 pentamidine, 172 nDEF, 335 physical (see Physical enhancement) PARTRAC code, 336 radiation-induced DNA repair, 172 physical enhancement in biological systems, radiosensitization, 161 332, 333 type 1, 163–164 radiosurgery, neovascular age-related type 2, 164–165 degeneration, 334 X-ray irradiation, 162, 269, 270 role of colloidal gold, 332 X-ray nanochemistry, 270 X-ray energy, 336 Biological systems, 4 Cancer-bearing animal models, 372 Biology, 247, 248 Cancer-bearing mice, 321, 367 Biomolecules, 274 Cancer (in vitro) cell lines, 344–362 nucleotides (see Damage to nucleotides) damage to tumors (see Damage to parameters, NMs, 271, 272 tumor cells) proteins, 272, 273 survey, 338–344 Bio-orthogonal chemistries, 311 uptake and enhancement data, 362 Biophysical model, 96 Cancer treatment, 16 Bismuth nanomaterial, 326 Capillary phantoms, 335, 336 Bismuth nanoparticles, 171, 210, 355, 376, 377 Catalysis, 24 Bismuth oxide nanoparticles, 359 chemical enhancement, 423–427 Bisphosphate-functionalized gold CO2 reduction, 412 nanoparticles, 325, 328, 329 conventional heterogeneous catalysis, 414 Blood-brain barrier, 321 exploration of, 411 BM@NCP(DSP)-PEG, 222, 377 hydroxyl radicals, 128 Bovine aortic endothelial cells (BAECs), 288 nanoparticles Brachytherapy, 60, 91, 92 advantage, 126 Broad-spectrum sources, 91 DMPO, 127 Bromodeoxyuridine (BrdU), 7 gold, 128 BUdR, 301 properties, 127 5-tert-Butoxycarbonyl-5-methyl-1-pyrroline surface atoms, 126 N-oxide (BMPO), 81 pathways, fundamental chemical, 413 Index 499

Pd, 129 low-energy/solvated electrons, 151, 152 photocatalysis, 411 multiplication algorithm, 189, 190 superoxide radicals, 143 and nanobiology, 174 type 1 physical enhancement, 411 and nanochemical systems, 174 type 1/2 physical enhancement, 412 nanomaterials and experimental type 3 physical enhancement, 412 conditions, 160 X-ray irradiation, 129, 131, 132 7-OHCCA, 119 CdSe quantum dots, 344 and physical (see Physical enhancement) CdTe X-ray detectors, 316 polymerization, 119, 423 Ce3+-doped lanthanum(III) fluoride principles, 159 nanoparticles, 354 probing reactions, 178 Cell cycle synchronization (CCS), 172 small gold nanoparticles, 177 Cell division cycle, 173 T1CE and T2CE, 180, 182, 183 Cell killing by nanoscintillators, 102 type 1, 137, 423 Cell-penetrating peptides (CPPs), 69, 308, 311, hydroxylation (see Hydroxylation 312, 328, 353 reactions) Cell-penetrating peptide (CPP)-modified gold polymerization, 143, 144 nanoparticles, 356 ROS, 123, 135 Cell survival curves (CSC), 309, 310, 370 superoxide-enabled catalysis, 143 Cell survival fraction measurements, brain type 1/2, 171 tumor cells, 172 type 2, 145, 426, 427 Cellular damage, 163 ROS (see Reactive oxygen species (ROS)) Cellular surface components, 328 X-rays, 136 Cell work, medical applications X-ray irradiation, 165 advantages/disadvantages, 303 Chemiluminescence, 128 assays, 308 Chemoradiotherapeutic effect, 358 cell lines, 303–305 Chemoradiotherapy, 214 cell preparation, 303 Chest X-rays, 314 cytotoxicity, 309 Cisplatin-packed nanoliposomes, 370 endpoints, 308 Clinical trial enhancement measurements, 309–310 tumor (in vivo) tissues, 377–378 irradiation with X-rays, 309–310 Clonogenic assays, 308, 346, 358, 362 types of cells, 303–305 Clusters, 217 uptake, 305–308 CO2 reduction, 412, 414, 419, 423 Characterization of nanomaterials, 227, 228 Coherent X-ray imaging, 317 Chelate surfactants, 324, 369 Collision-based approach, 39, 94 Chemical enhancements, 12, 123, 125, 135, Collision-based methods, 34 136, 143, 144, 159 Colon cancer cells, 361 aniline, oxidation and polymerization, 424 Colorimetry, 450 anti-enhancement, 121–123, 162 Combination of individual enhancements application of, 426 addition algorithm in aqueous solutions, 174 absolute enhancement, 188 and biological effects, 160, 169 chemical probes, 185 catalysis, 162 (see also Heterogeneous experimental results, 186, 187 catalysis) physical enhancement, 184 3-CCA, 119 relative enhancement, 188 clue of existence, 118 volume fraction, 185 definition, 123 anti-enhancement, 193–195 EPR, 120, 121, 151 biological enhancement, 196 estimation, 424, 425 multiplication algorithm, 189, 191–193 gold nanoparticle-enhanced X-ray Compton electrons, 27, 31, 42, 57, 73, absorption, 120 88, 91, 100 H2 production, 426 Compton scattering, 3, 31, 32, 45, 49, hydroxyl radicals, 119, 121 56, 60, 72, 89, 338 ligand effects, 131 Computed tomography (CT), 314 500 Index

Conjugation ionizing radiation, 285 categories, 224 nanoparticles, 287 citrate anions, 224, 225 prokaryotic/bacterial cells, 291–293 covalent bonds, 224, 226 Damage to mitochondria, 285 DOX, 226 Damage to nucleotides PEGylated gold nanoparticles, 225 Auger electrons, 279 PVP, 224 brain tumor cells B16F10, 284 thiol ligands, 225, 226 citrate-covered gold nanoparticles, 277 Contrast agents, 391 DNA damage, 282 imaging and detection of tumors DOX, 282 articles, 327 DSBs, 274 before and after injections, 321, 324 LEE, 280 bismuth, 327 LEED, 281 bisphosphate-functionalized gold LEEEF, 280 nanoparticles, 325 low-energy electrons, 281 brain tumors in mouse brain, 321 platinum nanoparticles, 282 chelate surfactant layer, 324 polyelectrolytes, 283 core materials, 321–323 scDNA, 274–276, 279 CT imaging, phantom and juvenile solvated electrons, 281 swine, 324 SSBs, 274–276 CT planning, radiotherapy, 326 thiol undecane/DTDTPA, 281 glioma tumor-bearing mice, 327 Tris, 276, 277 gold nanoparticles, 321 X-ray-induced damage enhancement, 278, gold nanorods, 324, 325 280, 283 iron oxide nanoparticle-functionalized X-ray irradiation, 284 gold nanocages, 326 Damage to proteins, 272, 273 LaF3:Tb nanoparticles, 325 Damage to tumor cells liposomes, 327 bismuth nanoparticles, 355 micelle, 326, 327 bismuth oxide nanoparticles, 359 multimodal imaging approach, 325 cell viability/survival fraction, 361 nanodendrites, 326 chemoradiation therapy, 352 silica shell, 327 chemoradiotherapeutic effect, 358 single-walled carbon nanotubes, 326 CPP-modiﬁed gold nanoparticles, 356 surfactants, 327–329 CPP-PEG-AuNPs, 353, 354 and therapy enhancer, 324 cytotoxicity, 346 veins, 321 detection method, 359 X-ray imaging, 327 dicoblock copolymer PEG-PCL, 354 role of colloidal gold, 332 DNA repair proteins, 348 transmission electron microscope, 299 dose enhancement, 346, 347 Conventional heterogeneous catalysis, 414 Du-145 incubated, 345 Core-shell nanostructures, 37 dual ligand-coated gold nanoparticles, 349 Coumarin-3-carboxylic acid (3-CCA), 244 experimental measured enhancement, 344 Cu Kα X-ray source, 346 FeOx nanoparticles, 351 Cysteamine, 308, 345 foliate-conjugated gold nanoparticles, 355 Cytotoxicity, 26, 346, 386 formulation and survivability data, 352 measurements, 171 gadolinium nanoparticles, 359 medical applications, 309 Gd nanoparticles, 357, 358 Gd2O3 core and SiO2 shell, 362 gold nanoparticles, 344, 347, 348 D HeLa cells, 344, 356, 358 Damage to cells, 338, 340–343 HTB-72 skin melanoma, 361 eukaryotic human glioblastoma cells, 355 direct interaction, 286, 289 iron oxide nanoparticles, 354 indirect interaction, 290 K562 cells, 346 Index 501

lanthanide-doped ZnO-based nanoparticles Detection of nanomaterials, 314 and application, 360 tumors (see Imaging and detection of linear accelerators, 348, 349 tumors) low-dose-rate X-rays, 352 Dichloroﬂuorescein (DCF) assay, 357 lung cancer cell, 349 Dicoblock copolymer PEG-PCL, 354 MCF-7 breast cancer cell line, 345 Dihydroethidium (DHE), 118, 142, 244 MDA-MB-231 cells, 358, 359 5,5-Dimethyl-1-pyrroline N-oxide (DMPO), 127 MeV irradiation, 351 Dimethyl sulfoxide (DMSO), 83 mice tumor cells CT26, 345 Di-Se block copolymer, 387, 388 microbeam approach, 346 Dithiolated diethylene-triamine-pentaacetic microdisks, 355, 356 (DTDTPA), 281 MTT assay, 345 DNA damage/strand breaks and NAC, 359 electrophoresis, 242 Nanobiotix Inc., 346 DNA repairs, 4, 160 nanoscale energy deposition, 349, 350 DNA single-strand breaks (SSBs), 48 nuclear DNA damage, 347 Dose enhancement factors (DEFs), 12, 46, 47, pancreatic cancer cells, 357 71, 78, 88 PDT properties, 355 Dose enhancement ratios (DER), 12, 46, 337 PEGylated gold nanoparticles, 351 Dose enhancement units (DEU), 12, 13, 17, 46, pHLIP, 356 124, 466 photodynamic therapeutic agent, 354 Dosimetric reaction, 119 photofrin, 346 Dosimetric UV-Vis, 86 porphyrin, 356 DOSXYZnrc code, 332 prostate cancer, 350 Double-strand breaks (DSBs), 68 radiation enhancement, 350 Doxorubicin (DOX), 226, 282, 380, 387–389 radioprotectors, 360 Drug carriers, 391 radiosensitizers, 356 selenium particles, 357 silver-coated carbon nanoparticles, 353 E silver nanoparticles, 359 Earth oxide nanoparticles, 215 superparamagnetic iron oxide E. Coli, 170 nanoparticles, 355 Effect enhancement, 393 synchrotron X-rays, 345 EGSnrc, 91, 336 tantalum pentoxide, 354 Electron, 252 third-generation gold nanoparticles, 353 Electron-DNA resonance, 67 tiopronin-coated gold nanoparticles, 360 Electron emission tirapazamine-conjugated gold and energy deposition nanoparticles, 360 angular anisotropy, 41 titanium dioxide nanoparticles, 361, 362 collision-based approach, 39 titanium peroxide nanoparticles and core-shell nanostructures, 37 hydroxyl radicals, 358 electron relaxation/charge transfer U251 cells and 6 MV X-rays, 359 processes, 40 uptake and cell viability results, 345 from gold atoms, 38 uptake of nanoparticles, 347 hardening, 38 verteporﬁn, 361 intra-nanoparticle (or interatomic) electron WS2 nanodots, 361 excitation mechanism, 39, 40 X-ray energy range, 344 local and remote enhancement, 37 Decomposition, 432, 434, 437 low-energy electrons, 41 CO2, 444 Monte Carlo method, 39 hydrogen peroxide, 445, 446 plane metal samples and nanoparticles, 39 large molecules, 447 small nanoparticles, 37 Delivery of nanomaterials softening, 38 surfactants, 327–329 with X-rays, 38 502 Index

Electron emission (cont.) DNA damage/strand breaks and γ-rays (MeV X-rays), 41 electrophoresis, 242 after X-ray absorption electron and XPS, 252 anisotropic angular distribution, 30 EPR, 249, 250 from atoms, 30 ﬂuorescence, 243–246 Auger electrons, 29, 30 in situ detection, 260, 261 Auger process, 29 and irradiation with X-rays, 309–310 Compton scattering, 31, 32 methods, 240 elastic collisions, 31 MRI, 249 Geant4, 30 nanochemical and bacterial systems, 459 from gold atoms, 30, 31 NMR, 249 heavy elements and X-ray energies, 29 SERS, 247 inelastic collisions, 31 UV-Vis spectroscopy, 251 LLSG, 30 X-ray sources (see X-ray sources and pair production, 31, 32 instrumentation) photoelectrons, 29 Enhancement of X-ray effects, 6 photoionization process, 29 Environmental remediation, 432, 436, 452 secondary electrons, 30 nanomaterials Electron gamma shower (EGS) software protection reagents, 452 toolkit, 52 X-ray irradiation, 452 Electron-hole pairs, 72 poly(L-lactic acid), 451, 452 Electron paramagnetic resonance (EPR) radiocatalytic degradation, 451 spectroscopy, 81, 84, 120, 121, 148, Epidermal permeation and retention (EPR) 149, 240, 249, 250, 262 effect, 311 Electron relaxation/charge transfer processes, 40 ESGnrc, 62 Electrons depositing energy, 12 ESRF synchrotron source, 380 Electron spin resonance (ESR), 148, 240, 436 Ethylene diamine tetra acetic acid (EDTA), 440 Endothelial cell-targeting gold nanoparticles, 58 Eukaryotic cells Endpoints, 309, 346, 356 biodistribution data, 166 and assays, 308 DEU enhancement, 169 Energetic Auger electrons, 70 direct damage Energy dependency, 61 BAECs, 288, 289 Energy deposition, 24, 337 epithelial cells, 289, 290 electron interactions with matter MCF-10A, 286, 287 boron and indium, 34, 35 monochromatic X-rays, 289 collision-based methods, 34 X-ray nanochemistry, 286 formula-based approach, 34 experimental enhancement measured, 167 NOREC package, 34 gold loading in mice, 166, 167 ratios, 34 gold nanoparticles, 166, 167 secondary X-ray ﬂuorescence, 34 indirect damage, 290, 291 secondary X-ray photons, 34 ligand-conjugated gold nanoparticles, 168 stopping power, 34 radiotherapy, 169 in water/other media, 36 thioglucose-bound gold nanoparticles, 168 Energy deposition density (EDD), 74, 75 TiO2 nanoparticles, 169 Energy deposition processes, 43 ultrasmall gold nanoparticles (Au29–43), Energy-dispersive detectors, 319 radiotherapy, 169, 170 Enhancement algorithm, 189 X-ray energies range, 169 See also Combination of individual European Synchrotron Research Facility enhancements (ESRF), 324 Enhancement computation, 309, 310 Europium-doped gadolinium oxide (Eu3+: Enhancement measurements Gd2O3) nanoparticles, 104 animal models, 240, 241 Experimental investigations biological enhancement, 269, 270 physical enhancement biology, 247, 248 calibrations, 70 Index 503

categorization, 63, 64 aqueous solutions, 243 CPPs, 69 3-benzoic acid, 244, 245 DNA under X-ray irradiation, 68 3-CCA, 244 energy deposition by lead, 68, 69 CT principles, 317 gel electrophoresis, 68 DHE, 244 gold nanotube enhancement, DNA single photon detection, 243 strand breaks, 66, 67 SRB, 245 indirect methods, 69 X-ray photovoltaics, 245, 246 in vitro/in vivo, 63 Foliate-conjugated gold nanoparticles, 355 measured enhancement values, 63 Fourier transformation measurements, 63, 64 transmission imaging, 318, 319 mechanisms of DNA damage, 67, 68 Fourier transformed images, 317 metal nanoparticles/bulk materials, 67 Fourier Transform Infrared (FTIR) nanomaterials, 65 spectroscopy, 359 polyelectrolyte surfactants, 69 Fourth-generation synchrotron sources, 8 radiosensitization study, 69 resonance interactions, 67 SSBs, 66 G Tris/EDTA, 66 Gadolinium (Gd) nanoparticles, 61, 357–359 tumor suppression report, 65, 66 Gadolinium ions vs. gadolinium T1PE, 79–81 nanoparticles, 40 T2PE, 95–97 Gas phase samples, 35 Experimental measurements, T3PE GEANT4, 30–32, 34, 39, 52, 54, 55, 57–59, 61, CdTe and ZnO, 102 62, 78, 336, 465, 466, 468, 470 cell killing by nanoscintillators, 102 Gel electrophoresis, 68 3+ LaF3:Tb , 101 Glioblastoma tumors, 373 lanthanide micelles, 104 Glioma tumor-bearing mice, 327 lanthanide nanoparticles, 103 Glucose-coated gold nanoparticles, 344 molybdenum cluster-based nanoscintillator, Glucose-covered gold nanoparticles, 345 105 Gold-chitosan nanocomposites, 148 Nanobiotix Inc., 102 Gold nanoparticles (GNP), 26, 56, 57, nanocrystals, 102 92, 163, 164, 299 nanoscintillator-based singlet oxygen 3, 7, and 30 nm, 206 generator, cell killing, 102, 103 PEGylated, 206 photodynamic therapy, 101, 105 radiotherapy, 205, 207 rare earth nanoparticles, 102 seed growth method, 208 self-lighting photodynamic therapy, 101 sizes and coatings, 205 singlet oxygen, 102 small nanoparticles, 205 TAT ligands, 102 synthesis and self-assembly, 204 XEOL, 101 TMA ligands, 206 X-ray-absorbing, 101 X-ray irradiation, 178 X-ray-and light-induced X-ray nanochemistry, 204 photoluminescence, 104 Gold nanoshells, 383 X-ray-induced ﬂuorescence in Eu3+-doped Graphene oxide quantum dots (GQD), 222 Gd2O3 nanoparticles, 104, 105 Extended X-ray absorption ﬁne structure (EXAFS), 154 H γ-H2AX assay, 375 H460 cells, 346 F Hafnium oxide nanoscale crystallites, 102 FePt nanoparticles, 317 Hardening, electron emission, 38 Figure of merit, 57 Heavy elements, 27 First-generation nanomaterials, 460 HeLa cells, 171, 312, 344, 353, 356 Fluorescence to FePt nanoparticles, 358 APF, 244 radiotherapy, 355 504 Index

HepG2 cells (human liver cancer cells), 81 contrast agents (see Contrast agents) Heterogeneous catalysis, 126–128, 130, 131 CT, 314 catalytic radiolysis, CO2/water, 419 ICP-MS, 330 conventional heterogeneous catalysis, 414 LD50 toxicity level, 331 CO production from CO2, 420, 421 mass attenuation coefficients, 330 CO2 reduction reaction pathways, 414 mass energy absorption coefficients, 330 CO2 on zeolites, decomposition of, 420 methods definition, 418 APS, 316 Fenton reaction, 129 CdTe photodiode detector, 315 gold nanoparticle oxidation, CO to CO2, 414 CdTe X-ray detectors, 316 hydrogen peroxide, decomposition of, 414 coherent X-ray imaging, 317 for metallic surfaces, 415 CT imaging, 317, 318 nanoparticles FePt nanoparticles, 317 advantage, 126 fluorescence CT principles, 317 DMPO, 127 Fourier transformation, transmission gold, 128 imaging, 318, 319 properties, 127 gold nanoparticles in tumor phantoms, size and shape effect, 130 319, 320 surface atoms, 126 nanoparticle-enhanced X-ray imaging, surfactant effect, 131 315 photocatalysis, X-ray, 415 NIR imaging, 318 SPR, 418 phantoms, 316 X-ray dose-rate dependency, 134, 135 scanning beam digital X-rays, 317 X-ray energy dependency, 134 silica-coated gold nanorods, 315, 316 X-ray generated electron-hole pairs and UWPCI, 315 radicals, 419 UWPSN, 315 X-ray irradiation, 129 XFCT, 316, 317 Heterogeneous multiscale (HetMS) model, 52 X-ray fluorescence, 315, 319, 320 HfO2 nanocrystals, 346 MRI, 314 7-Hydroxycourmarin 3-carboxylic acid nanomaterial-assisted X-ray imaging, 330 (7-OHCCA), 119 nanoparticle-enhanced X-ray imaging, Homemade program, 55 330, 331 Homogeneous catalyst, 126 number of publications, 314 HTB-72 skin melanoma, 361 objects, 321 Human glioblastoma cells, 355 PET, 314 Human serum albumin (HAS), 381 units of WP, 330 HVGGSSV peptide ligands, 317 XIET, 314 Hydroxylation reactions X-ray attenuation, 314 DNA strand break X-ray treatment, 331 gold nanoparticles, 137, 138, 140, 141 Indirect methods, 69 monochromatic X-rays, 140, 141 Inductively coupled plasma mass spectrometry phosphodiester linkage, 137 (ICP-MS), 305 scDNA, 139 Inelastic collisions, 31 Tris-dependent enhancement, 138, 140 In situ detection 7-OHCCA, 136 ERP, 261 small molecules, 141, 142 X-ray photovoltaics, 261 Hydroxyl radicals, 66, 67, 80, 81, 83, 85, 86, Instrumentation, 239, 459, 461 97–99, 387 Interatomic excitation/de-excitation, 28 Intra-nanoparticle collision mechanism, 94 Intra-nanoparticle (or interatomic) electron I excitation mechanism, 39, 40 ICP-MS, 330 Intra-nanoparticle electron relaxation Imaging and detection of tumors processes, 41 Index 505

In vivo luminescent nanoparticles, 101 Linac Coherent Light Source (LCLS), 8 Iodine-based contrast agent, 326 Linear-quadratic model (L-Q), 370 Iodine labeled nucleotides, 299 Liposome encapsulated perfluorohexane, 385 Iododeoxyuridine (IUdR), 7, 299, 301 Liposome-enclosed doxorubicin (DOX), 387 Ionizing radiation, 24, 299 Liposomes, 211, 327 artificial chemical/nanochemical systems, 4 Local effect model (LEM), 52, 58, 92, biological systems, 4 93, 96, 97, 337, 338, 359 Compton scattering, 3 Low operating voltage, 171 detection, 432 Low-energy electron depositing energy, 72 DNA repair, 4 Low-energy electron diffraction (LEED), 281 electrons in atoms, 3 Low-energy electrons (LEE), 279 light elements, 4 Low-energy X-rays, 171 with nanomaterials, 6 Low-linear energy transfer (LET) ionizing photosynthesis, 4 radiation, 13 radioresistive bacteria, 4 and γ-rays, 3 types, 3–6, 13–15 M and X-rays, 3, 13–15 Macroscopic dose enhancement factors Iron oxide nanoparticles, 354 (mDEFs), 55 Irradiation protocols, 313 Macroscopic enhancement, 92 Isolation and optimization Magnetic resonance imaging (MRI), 249, 314 biological enhancement, 179, 183 Mass attenuation coefficients, 28, 29, 32, 33, chemical enhancement 36, 44, 46, 57, 330 type 1, 182 Mass energy absorption coefficients, 28, 29, 32, type 2, 183 33, 35, 36, 44, 57, 330 physical enhancement Mass spectrometry, 305, 312 type 1, 179, 180 Mathematica, 469, 471, 474, 479 type 2, 179, 181 C++ program, 466, 470 type 3, 179 geometric shapes, 471 T1PE, 476, 477 T2PE, 473, 475, 476 J visualization and implementation, 466 Jejunal crypts, 370 MCF-7 breast cancer cell line, 345 MCNPX, 54, 58 MDA-MB-231 cells, 338, 359 K Mean dose enhancement factors (MDEFs), 95 KB cells, 383 Medical applications, 303–314, 338–363 keV X-rays, 102 animal work (see Animal work, medical applications) cancer treatment, 302, 331–338 L cell work (see Cell work, medical Lanthanide (Gd and other elements)-doped applications) titania nanoparticles, 371 chemistry and biology laboratories, 300 Lanthanide micelles, 104 clinical trials, 300 Lanthanide nanoparticles, 103 clinical work, 313 Lattice effect, 337 component nanomaterials, 391 LEE enhancement factor (LEEEF), 280 damaging cells/treating tumors, 300 Lee-Lu-Sharmah-Guo (LLSG), 30, 52, destruction of cells, 300 78, 465, 479 gold nanoparticles, 300 Lewis lung carcinoma, 370 imaging and detection of tumors (see 9L gliosarcoma-bearing rats, 369 Imaging and detection of tumors) Ligand effects, 131 ionizing radiation, 299 Ligand stability, 227 IUdR, 299 506 Index

Medical applications (cont.) MTT assay, 345 nanomaterial-assisted radiation therapy, 392 Multiplication algorithm of enhancements nanostructures, 391 chemical enhancement, 189 NEXT, 299, 300 silica-coated gold nanoparticles, 189, 190 photodynamic therapy, 391 T1CE, 191, 192 photothermal therapy, 391 T1PE, 190, 192 physical enhancement, 302 THPC-coated gold nanoparticles, 190 quantum dots, 390 X-ray dose rate, 189 radiation sensitizers, 391 Murine squamous cell carcinoma, 367 radiosensitization, 301, 392, 393 MV X-rays, 332, 373 radiosensitizers, 391, 392 radiotherapy, 299, 301, 390 treatment (see Treatment, medical N applications) N-acetyl cysteine (NAC), 359 X-ray-triggered release, 386–389 Nanoassembly, 221 Medical X-rays, 55 Nanobiology, 174, 462 Mercaptopropionic acid (MPA), 206, 216 Nanobiotix Inc., 102, 346 Mesoporous tantalum oxide nanoparticles, 385 Nanochemical environments, 17 Metal implants, 25 Nanochemistry, 3, 5–6 Metal nanoparticles, 67, 131, 133 component, 9 3-Methyladenine (3-MA) autophagy development, 7 inhibitor, 359 X-ray (see X-ray nanochemistry) 4-Methylthiophenylmethanol (MTPM), 424, 425 Nanodendrites, 326 MeV medical X-rays, 55 Nanoliposomes, 370 MeV photons, 61 Nanomaterial-adding biological systems, 174 MeV radiation, 386 Nanomaterial-assisted radiation therapy, 392 Micelle, 326, 327 Nanomaterial-assisted X-ray imaging, 330 Microbeam approach, 346 Nanomaterial-assisted X-ray treatment, 379 Microdisks, 355, 356 Nanomaterial C-Ag-PEG, 353 Microfocus X-ray source, 388 Nanomaterial-enhanced radiotherapy, 387 Micron-sized gold particles, 26 Nanomaterials, 37–43 Microscopic dose enhancement factors advantages, 301 (mDEFs), 12, 88, 91, 93 in biological systems, 17 Mitochondrion, 94 in cancer treatment, 7 Molybdenum cluster-based nanoscintillator, 105 development, 7 Monochromatic kilovoltage X-rays, 336 exotic functions, 5 Monte Carlo (MC), 54, 66, 78 heavy elements, 14 algorithm, 52, 54, 66, 78 ionizing radiation, 3, 6 method, 39, 52, 55, 57, 316, 338 production, 6 program simple, man-made/engineered, 5 enhancement calculation, 472, 473 surface chemistry, 10 Geant4 code, 465 synthesis, 6, 7, 18 generic variables, 471 types of radiation, 13 ionizing radiation, 465 X-ray absorbing, 12, 16 LLSG, 466 X-ray imaging, 15 Mathematica, 471 X-ray interactions program components, 470 electron emission and energy simulation method, 466, 468, 469 deposition, 37–41 T1PE, 476, 477 scintillation and photon emission, 41–43 T2PE, 473–476 X-ray nanochemistry, 15 Monte Carlo N-Particle (MCNP) code, 54 X-ray synthesis, 15 MTS assay, 361 Nanomaterials for enhancement MTS cell viability assay, 381 anti-enhancement, 231 Index 507

biological enhancement, 232 P chemical, 230 Palladium-103 brachytherapy radioisotope, 385 electron retention, 201 Palladium-coated hollow gold nanoparticles, 213 gold nanoparticles, 201 Pancreatic cancer cells, 357 parameters, 203 PARTRAC, 54 particle size, 201, 202 PEG-coated gold nanoparticles, 81 physical PEGylated AuNR (PEG-AuNR), 373 type 1, 228 PEGylated gold nanoparticles, 97, 373 type 2, 229 PEI-AuNPs, 381 type 3, 230 PENELOPE, 52, 54, 55, 336 properties, 202, 203 PENELOPE-2011, 62, 336, 384 X-ray nanochemistry, 232 Pentakis(dimethylamido)tantalum Nanoparticle-enhanced X-ray imaging, 315, (PDMAT), 418 330, 331 Pentamidine, 172 Nanoparticle-enhanced X-ray therapy Peptide-conjugated nanoparticles, 380 (NEXT), 299, 300 Perfluorocarbons (PFCs), 385 Nanoparticles, 26 Phantoms, 316 Nanoreactors, 17 Pharmacokinetics, 312 Nanoscale dose enhancement factors 2-Phenylthioethanol (PTE), 424 (nDEFs), 12, 87 pH low-insertion peptide (pHLIP), 308 Nanoscale energy deposition, 12, 55, 70, 87 Photo-activated therapy (PAT), 371 Nanoscale enhancement, 88, 89 Photocatalysis Nanoscale physical enhancement, 12 and chemical-driven catalysis, 418 Nanoscience, 7 in copper oxide nanoparticles, 423 Nanoscintillators, 42, 375 definition, 415 Nanoseeds, 385 fundamental chemical pathways, 414 Nanotechnologies, 7 homogeneous/heterogeneous, 415 Narrow beam irradiation configuration, 59, 60 nanomaterials, 411, 421, 422 National Institute of Standards and Technology of splitting water, 415 (NIST), 54 step of, 415 National Nanotechnology Initiative (NNI), 5 type 2 chemical enhancement, 412 NBTXR3, 102, 103 typical process, 416 Near-infrared (NIR) imaging, 318 vs. X-ray catalysis, 416 Ne-Kr cluster system, 40 X-ray vs. regular photochemistry, 416 Neovascular age-related degeneration, 334 Photodynamic therapy (PDT), 101, 105, 355, Neutral gold nanoparticles, 344 388, 391 Nonmalignant breast cancer cell line Photoelectric effect, 29, 31 (MCF-10A), 286 Photoelectrons, 29, 30, 55, 70, 94, 171, 334 Nonphysical processes, 24 Photofrin, 346 Nonspherical nanoparticles, 218, 219 Photoionization process, 29 Nonuniform enhancement, 58 Photoluminescence spectra, 104 NOREC, 34, 52, 54, 55, 78, 91, 465, 466, 470 Photon emission and scintillation, 41–43 Nuclear dose enhancement factor (nDEF), 61, Photosynthesis, 4 94, 95, 335 Photothermal therapy, 391 Nuclear localization signal (NLS) peptide, pH-sensitive low-insertion peptide (pHLIP), 356 311, 312 Physical enhancement, 11, 12, 28–35, 70, 117 Nuclear magnetic resonance (NMR), 249 absolute and relative, 46 absorption of X-rays, 47 advantages, 160 O biological mechanisms, 161 Optimal scintillation processes, 105 in cells, 160 Organometallic nanoparticles, 337 and chemical, 124, 125, 159, 160, 163, 174 Oxidative stress, 272, 290 definition, 24, 44–46 Oxide nanoparticles, 214 DEU, 167, 168 508 Index

Physical enhancement (cont.) Probabilistic approach, 62 directness and linearity, 24 Probe reactions, 178 energy deposition, 24 Prokaryotic/bacterial cells damage, 291–293 experimental investigations, 63–70 Properties of nanomaterials, 202, 203 experimental works, 47–49 Prostate cancer cells (PC3), 67, 344, 354 history, 25–27 Protein damage mechanisms, 273 ionizing radiation, 24 Protein disulﬁde isomerase (PDI), 164 isolation, 161 Proton therapy, 299 large gold nanoparticles, 177 Pseudomonas aeruginosa, 170, 171 motivations, 24–25 Pt compounds, 367, 368 nanomaterials and experiments, 173 Pulsed X-ray sources, 461 nonphysical processes, 24 physical principles, 465 principles, 159 Q process of X-ray absorption, 43 Quantum dots, 5, 216, 390, 447 secondary ﬂuorescence, 46, 47 T1PE (see Type 1 physical enhancement (T1PE)) R T2PE (see Type 2 physical enhancement Radiation chemistry, 14 (T2PE)) Radiation-guided nanoparticle drug delivery T3PE (see Type 3 physical enhancement system, 380 (T3PE)) Radiation-induced DNA repair, 172 theoretical packages, 52–54 Radiation protection, 452 theoretical simulation, 48–49 Radiation sensitizers, 391 thick samples, 47 Radiolabeled iododeoxyuridine (IUdR), 26 tumor loading, 166 Radiolysis type 1, 164, 165 assisted by nanomaterials, 444, 445 type 2, 164, 165 ionizing radiation, 433 type of electrons in atoms, 27 molecules, 434, 435 units, 46 nanomaterials, 435 XPS, 44 γ-rays, 432 X-ray absorption, 24 X-rays, 431, 433, 434 X-ray-generated species, 23 Radiolysis with X-rays X-ray imaging, 44 CO2, 444, 445 X-ray interactions (see X-ray interactions, heterogeneous catalysis, 437 physical enhancement) hydrogen X-ray irradiation, 23 catalytic properties, 438 Plasmonic nanobubbles, 382 gold nanoparticles, 440, 441 Platinum nanoparticles, 149, 150, 209 nuclear plants/waste containers, 437 Poly acrylic acid (PAA) ligands, 352 γ-ray irradiation, 440, 443, 444 Poly(methyl methacrylate) (PMMA), 316 TiO2 and Al2O3, 437, 438 Polyaniline shell, 385 Zeolite structures, 437, 443 Polyelectrolyte ligands, 308 ionizing radiation, 442 Polyelectrolyte surfactants, 69 solvated electrons, 442, 443 Polyethylene glycol (PEG), 206, 317, 353 water Polyethylenimine (PEI), 381 CeO2 and ZrO2, 438, 439 Polylactide-glycolide microparticles, 387 nanoporous gold, 439 Polymerization, 143, 144 silica gel, 440 Polymer-linked cisplatin compound shell, 377 silica nanoparticles, 441 Polymethylmethacrylate (PMMA), 26 silica nanostructures, 439 Porphyrins, 356, 367 Radiophotodynamic therapy (RPDT), 104, 356 Position-sensitive energy deposition, 87 Radioprotectors, 360 Positron emission tomography (PET), 314 Radioresistive, 4, 170 Preclinical trial Radiosenisitizers, 392 tumor (in vivo) tissues, 377–378 Radiosensitization, 69, 161, 392, 393 Index 509

Radiosensitizing property, 376 Silica-coated gold nanoparticles, 80 Radiosensitizers, 356, 361, 382, 386, 390, 391 Silica-coated gold nanorods, 315, Radiosurgery, 334 316, 318, 376 Radiotherapeutic effect Silica-covered gold nanoparticles, 211 ultrasmall gold nanoparticles, 373, 374 Silica-covered large gold nanoparticles, 83–84 Radiotherapy, 9, 17, 55, 161, 169, 299, 301, 390 Silica shell, 327 gold nanoparticles, 390 Silicon carbide/silica (SiC/SiOx) nanowires, 356 planning, 381 Silicon and germanium semiconductor, 216 Rare earth element-doped TiO2 Silver-coated gold nanoparticles, 213 nanoparticles, 371 Silver-core-gold-shell nanoparticles, 210 Rare earth nanoparticles, 102 Silver nanoparticles, 209, 359 γ-Ray irradiation, 387 Simulation of enhancement, 319, 331, γ-Rays, 13 333, 336, 359, 381 Reactive oxygen species (ROS), 339 Single-photon emission computed tomography chemical enhancement, 146 (SPECT), 385 decreasing process/anti-enhancement, Single-strand breaks (SSBs), 66, 68, 194, 148–151 275, 276 gold nanoparticles Singlet oxygen, 101, 102, 387 increased production, 145 Singlet oxygen production, 375 superoxide radicals, 146 Singlet oxygen sensor green (SOSG), 101 X-rays, 147 Single-walled carbon nanotubes, 326 increased production, 145, 147 Softening, electron emission, 38 scavenging reactions, 358 Spherical nanoparticles, 87 silicon nanoparticles, 146 bismuth nanoparticles, 210 Relative biological effectiveness (RBE), clusters, 217 58, 78, 92 earth oxide nanoparticles, 215 Relative enhancement, 12, 45 gold nanoparticles Relative physical enhancement, 46 3, 7, and 30 nm, 206 Resonance interactions, 67 PEGylated, 206 radiotherapy, 205, 207 seed growth method, 207 S sizes and coatings, 205 Scanning beam digital X-rays, 317 small nanoparticles, 205 Scavenging radicals, 360 synthesis and self-assembly, 204 Scintillation, 72, 100, 101, 367 TMA ligands, 206 and photon emission, 41–43 X-ray nanochemistry, 204 Scintillators, 101 liposomes and calcium phosphate, 211 Secondary charged particles, 27 oxide nanoparticles, 214 Secondary electrons, 30 palladium-coated hollow gold Secondary X-ray ﬂuorescence, 34 nanoparticles, 213 Secondary X-ray photons, 32–34 platinum nanoparticles, 209 Self-lighting photodynamic therapy, 101 quantum dots, 216 Semiconductor nanomaterials, 72 selenium-selenium polymer, 217 Sensing, 433, 436 silica-covered gold nanoparticles, 211 EPR detection, 447 silicon and germanium semiconductor, 216 gold nanoparticles, 447, 449, 450 silver-coated gold nanoparticles, 213 nanomaterials, 448 silver-core-gold-shell nanoparticles, 210 polysilanes, 447 silver nanoparticles, 209 quantum dots, 447 transition metal oxide nanoparticles, 214 SPR, 450 Spin trap reactions, 81 XIET, 451 Stanford Linear Accelerator Center (SLAC), 52 Sensitivity enhancement ratios (SERs), 95 Steep decay of enhancement, 58 SiBiGdNP, 377 Stopping power, 34 510 Index

Sulforhodamine B (SRB), 81, 97, 98, RBE, 92 181, 221, 245 SERs, 95 Supercoiled DNA (scDNA), 139 surface of spherical nanoparticles, 89, Supercoiled plasmid DNA (scDNA), 68, 274 91, 92 Superoxide dismutase (SOD), 119 Theoretical packages, physical enhancement, Superparamagnetic iron oxide nanoparticles, 355 52–54 Surface-enhanced Raman spectroscopy Theoretical simulations, physical enhancement (SERS), 209, 211, 247 BEAMnrc code, 61 Surface plasmon resonance (SPR), 251, 359, brachytherapy, 60 418, 450 calculation, 56, 59 Surfactants, 223, 311, 327–329 arrangement, 61 Synchrotron X-rays, 345, 371 programs and packages, 48 Synthesis of nanomaterials, 204, 460 directly measuring electrons, 48 aggregated, 220 by endothelial cell-targeting gold complex, 221, 222 nanoparticles, 58 nonspherical, 218, 219 energy dependency, 61 spherical (see Spherical nanoparticles) figure of merit, 57 Geant4 code, 59, 61 homemade code, 62 T homemade program, 55 Targeted gold nanorods (AuNR), 373 Mathematica program, 55 Targeting MCNP code, 61 gold nanorods (AuNR), 328 MCNPX code, 58 medical applications, animal work, 311–312 mDEFs, 55 surfactants, 327–329 medical X-rays, 55 tumor cells and damage, 339 MeV photon irradiation, 58 Tb-doped LaF3 nanoparticle-rose bengal microbeam configurations, 61 (RB) composites, 104 Monte Carlo method, 57 Terpyridine-coordinated platinum ions, 172 nanomaterials, 62 Theoretical calculations nanometer-wide X-ray beams, 59, 60 T1PE, 76–79 nanoscale energy deposition, 55 T2PE nDEF, 60 average energy deposition density, 89 nonuniform enhancement LEM, 58 calculated energy deposition, 94 PENELOPE method, 55 circular and elliptical two-dimensional principle of calculation, 49 cell shapes, 95 probabilistic approach, 62 energy deposition profile, 89 ratio of energy deposition, 49 gold nanoparticles and electrons RBE, 58 produced in water, 89, 91 reports, 49–51 groups, 89, 90 resonant X-ray absorption, 58 intra-nanoparticle collision steep decay of enhancement, 58 mechanism, 94 type of ionization, 57 LEM, 92, 93 XIET, 56, 57 location dependency, 94 X-ray and γ-ray irradiation, 60 magnitude, 89 Thermal drugs, 391 mDEFs, 91, 93, 95 Thin and thick bulk solid samples, 35–37 measurements, 89 Thin-film photovoltaic cells (TFPCs), 105 nanoscale energy deposition, 92 Thiol ligand coverage approach, 225 nanoscale enhancement, 89 Thomson scattering process, 31 nanostructures and nanoparticle Tiopronin-coated gold nanoparticles, 360, 376 aggregates, 89 Tirapazamine, 360 nDEF, 94, 95 Titanium dioxide (TiO2) nanoparticles, 361, outcome, 95 362, 384 Index 511

Tool for Particle Simulation (TOPAS), 54 radiation therapy, 378, 379 TOPAS-nBIO, 54 survey of in vivo work Toxicity, 436 A375 cell line and A375-bearing Transition metal oxide nanoparticles, 214 mice, 376 Transmission electron microscopy (TEM), 96 amphiphilic dicoblock copolymer poly Treatment, medical applications, 338–385 (ethylene glycol)-b-poly cancer (ε-caprolactone) PEG-b-PCL, amplification, 382, 383 373, 374 arc radiation therapy, 384 Au@MnS@ZnS-PEG, 375 Auger processes, 380 Balb/C mice, 363 Au@MnO2-PEG, 384, 385 biodistribution measurements, 377 continuous scanning focusing X-ray bismuth nanoparticles, 376, 377 needle beam, 381 BM@NCP(DSP)-PEG, 377 dose enhancement, 382 cancer-bearing mice, 367 dose profile, 381 chelate surfactants, 369 doxorubicin, 380 cisplatin-packed nanoliposomes, 370 gold nanoshells, 383 enhancement of radiation damage, KB cells, 383 363–366 liposome encapsulated Gd2O3 core and SiO2 shell, 377 perfluorohexane, 385 glioblastoma tumors, 373 mesoporous tantalum oxide Jejunal crypt survival curves, 370 nanoparticles, 385 lanthanide-doped titania nanoparticles, nanomaterial-assisted X-ray 371 treatment, 379 9L gliosarcoma-bearing rats, 369 NIR irradiation, 384 mice treated, 367, 368 palladium-103 brachytherapy MRI, 369, 370 radioisotope, 385 murine squamous cell carcinoma, 367 PEI-AuNPs, 381 MV X-rays, 373 PFCs, 385 nanoliposomes, 370 radiation-guided nanoparticle drug nanoscintillator, 375 delivery system, 380 PAT, 371 radiotherapy planning, 381 PEGylated gold nanoparticles, 373 S2 cells, 381 Pt compounds, 367, 368 silica-coated rare earth nanoparticles, 383 radiosensitizing property, 376 TiO2 nanoparticles, 384 rare earth element-doped TiO2 UCNPs, 384 nanoparticles, 371 USMS-SNO, 384 RGD peptides, 376 WS2 nanodot core, 385 scintillation, 367 X-ray beams, 380 SiBiGdNP, 377 cancer (in vitro) cell lines (see Cancer silica-coated gold nanorods, 376 (in vitro) cell lines) singlet oxygen production, 375 tumor (in vivo) tissues (see Tumor (in vivo) synchrotron X-rays, 371 tissues) targeted gold nanorods (AuNR), 373 Trimethylammonium (TMA) ligands, 150, 193 tiopronin-coated gold nanoparticle, 376 Tris(hydroxymethyl)aminomethane/ tumor-bearing animal model, 373 ethylenediaminetetraacetic acid ultrasmall gold nanoparticles, 373, 374 (Tris/EDTA), 66 X-rays and FeOx nanoparticles, 372 Tris scavengers, 96 Tumor loading, 166 Tumor-bound nanoparticles, 355 Two-photon excitation, 359 Tumor growth delay (TGD), 370 Type 1 biological enhancement, 12 Tumor (in vivo) tissues gold nanoparticle, 163, 164 clinical trial, 377–378 indirect enhancement, 163 preclinical trial, 377–378 nanomaterials, 164 512 Index

Type 1 biological enhancement (cont.) U nanoparticles, 163, 164 Ultrasmall gold nanoparticles Type 1 chemical enhancement, 12 radiotherapeutic effect, 373, 374 Type 1 physical enhancement (T1PE), 12, 411, Unit weight percent contrast increase 412, 416, 423, 425, 427 (UWPCI, 315 definition, 70–76 Unit weight percent signal-to-noise ratio (S/N) detection, 81 (UWPSN), 315 dosimetric UV-Vis, 86 Upconversion nanoparticles (UCNPs), 384 EPR spectroscopy, 84–86 USMS-SNO, 384 experimental investigations, 79–81 UV-Vis light, 12 isolation and optimization, 180 UV-Vis photons, 73, 100 LLSG, 476, 477 UV-Vis spectroscopy, 251 magnitude, 71 silica-covered large gold nanoparticles, 83–84 V theoretical calculations, 76–79 Verteporfin, 361 WP, 71 Vessel-targeted gold nanoparticles, 374 Type 2 biological enhancement, 12 bacterial DNA damage, 165 cell damage/death, 164 W damaging prokaryotic cellular DNA, 165 Wound healing, 346 deposit energy, 164 WS2 nanodots, 361, 385 gold nanoparticles, 165 mechanism, 164 mitochondria/nuclear DNA, 164 X nanomaterials, 164 X-ray-absorbing, 73, 101 size/mass of DNA, 165 X-ray absorption Type 2 chemical enhancement, 12 atomic number (Z) dependency of, 27 Type 2 physical enhancement (T2PE), 12 direct and linear response, 27 CaPEL nanoscale probes, 181 electron emission after, 29–32 characteristics, 87 by nanomaterials, 27 definition, 70–74, 87–88 secondary X-rays photon emission, 32, 33 experimental investigations, 95–97 X-ray fluorescence, 32, 33 isolation and optimization, 180 yttrium oxide nanoscintillators, 102 LLSG, 473–476 X-ray absorption near-edge structure magnitude, 87 (XANES), 144 spherical nanoparticles, 87 X-ray absorption spectroscopy (XAS), 240 theoretical modeling and calculations, X-ray activated catalysis 89–95 chemiluminescence, 128 XIET, 87, 98–99 gold nanoparticles, 127 Type 3 physical enhancement (T3PE), 12 ROS, 131, 132 definition, 70–74 X-ray-activated prodrugs, 17 exceptions, 106 X-ray attenuation experimental measurements, 101–105 by atoms and compounds gold nanoparticle-enhanced photodynamic algorithm, 33 system, 100 mass attenuation coefficients, 32, 33 measure and calculate, 100–101 mass energy absorption coefficients, 33 photons, 100 physical enhancement, 28–29 scintillation, 100 secondary X-ray photon emission, 32, 33 UV-Vis photons, 99, 100 types of interactions, 32 XOEL, 100 X-ray fluorescence after X-ray X-ray absorption, 99 absorption, 32, 33 X-ray-induced scintillation, 99 imaging and detection of tumors, 314 Index 513

X-ray beams, 79 medical applications (see Medical X-ray chemical biology, 174 applications) X-ray-driven catalytic reactions, 414, 415, nanomaterials, 17 (see also Nanomaterials) 417–419 nanoparticles and ionizing radiation, 6 X-ray excited optical luminescence (XEOL), nanoscience, 11 72, 100, 101 in nanosystems, 9 X-ray fluorescence, 315 number of publications, 10, 11 after x-ray absorption, 32, 33 photon energy, 462 X-ray fluorescence computed tomography principles, 6, 17, 339 (XFCT), 316, 317 properties, 17 X-ray fluorescent imaging, 319, 320 publications, 10 X-ray imaging, 44 radiotherapy, 17 X-ray-induced energy transfer (XIET), 56, 57, research area, 16 87, 97–99, 186, 314, 451 systematic study, 6 X-ray-induced radiophotodynamic therapy, 104 UC Davis, 7–8 X-ray-induced scintillation, 101 X-ray-activated prodrugs, 17 X-ray interactions, physical enhancement and X-ray nanobiology, 15 atoms and compounds and X-ray nanotechnology, 15 electron emission, 29–32 and X-ray synthesis, 15 energy deposition, 33–35 X-ray nano-prodrugs X-ray attenuation, 28 and X-ray-triggered released drugs, 386–389 nanomaterials, 37–43 X-ray nanotechnology, 9, 11, 15 thin and thick bulk solid samples, 35–37 X-ray photodynamic therapy, 103 X-ray irradiation X-ray photoelectron spectroscopy (XPS), 44, and enhancement measurements, 309–310 240, 252, 253, 461 nanomaterials, 159 X-ray photons, 29, 45 X-ray mass attenuation coefficients, 28 X-ray photovoltaics, 245, 246 X-ray nanobiology, 15, 174 X-ray scintillation/X-ray-induced X-ray nanochemical biology, 174 scintillation, 41 X-ray nanochemistry, 9, 126, 135, 143, 232, X-ray sources and instrumentation 239, 299, 411 bottom-up irradiation, 258 advantages, 13, 14 compact X-ray sources, 254 applications, 161 compton sources, 257 in catalysis (see Catalysis) filtered X-rays, 255 area of cancer treatment, 16 microfocus X-ray sources, 254, 256 Auger electron therapy, 17 scanning focusing, 260 BrdU, 7 sources and specifications, 259 catalysts and nanoparticles, 6 synchrotron X-rays, 256 concept, 9 top-down irradiation, 258, 259 definition, 6 X-ray synthesis, 6, 15 development, 7–10 X-ray-triggered release, 386–389 enhancement, 6 X-ray triggering mechanisms, 460 enhancement units, 11–13 implants, 7 instruments, 461 Y and ionizing radiation, 3–5, 13–15 Ytterbium nanoparticles, 327 IUdR, 16