Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis and Proton- and Electron-Induced DNA Damage in Computational Prototypes

Abstract

Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects. To overcome this situation, we are conducting time-dependent and non-adiabatic computer simulations of PCT reactions with the electron nuclear dynamics (END) method. Herein, we present a review of our previous and new END research on three fundamental types of PCT reactions: water radiolysis reactions, proton-induced DNA damage and electron-induced DNA damage. These studies are performed on the computational prototypes: proton + H2O clusters, proton + DNA/RNA bases and + cytosine nucleotide, and electron + cytosine nucleotide + H2O. These simulations provide chemical mechanisms and dynamical properties of the selected PCT reactions in comparison with available experimental and alternative computational results.

Multi-charged ion-water molecule collisions in a classical-trajectory time-dependent mean-field theory

“…Given the amount of water in the human body, the most likely event that occurs is the collision of the ion with a water molecule, which gives rise to different electronic processes such as the ejection of electrons, followed by further ionization or excitation processes [6]. Different mechanisms after the collision can cause DNA damage, such as the creation of secondary electrons and ions, of free radicals or the heating of the medium due to target excitation [7].…”

Proton-impact-induced electron emission from biologically relevant molecules studied with a screened independent atom model

“…While progress has been made on both experimental (see [2][3][4][5][6][7][8][9] for proton-impact collisions) and theoretical [10][11][12] fronts, the complexity and multitude of molecules of interest suggest that there is a role to be played by simplified models which are easily applicable to a wide range of collision systems.…”

“…and theoretical [10][11][12] fronts, the complexity and multitude of molecules of interest suggest that there is a role to be played by simplified models which are easily applicable to a wide range of collision systems.…”

Electron nuclear dynamics of time-dependent symmetry breaking in H+ + H2O at ELab = 28.5–200.0 eV: a prototype for ion cancer therapy reactions

“…We successfully applied SLEND to simulate various types of ICT reactions in systems involving H 2 O, DNA/RNA bases, and DNA nucleotides. 8,[21][22][23][24][25][26] For instance, we investigated H + + (H 2 O) n for n = 3-4 at E Lab = 1 keV 22,24 and for n = 1-6 at E Lab = 100 keV 23,24 to predict reactive processes and 1-ET ICSs. Herein, we study again H + + H 2 O, but we consider new conditions, properties, and phenomena.…”