# Tutorial on Energy Transfer Mechanisms and Computational Methods in X‑ray Photodynamic Therapy with Metal Nanoclusters

## TL;DR

This tutorial explains how metal nanoclusters can be used in X-ray photodynamic therapy to treat cancer by transferring energy to oxygen and generating toxic species.

## Contribution

The tutorial introduces metal nanoclusters as promising agents in X-ray photodynamic therapy and outlines current research gaps in energy transfer mechanisms.

## Key findings

- Metal nanoclusters, especially gold-based, show good biocompatibility and can function as photosensitizers in cancer treatment.
- X-ray photodynamic therapy offers potential due to high energy and low scattering in biological tissues.
- Current research lacks a full understanding of energy transfer mechanisms from nanoclusters to oxygen in photodynamic therapy.

## Abstract

Cancer remains the
deadliest disease for mankind, and hence, the
need for effective, reliable, and functioning cancer treatment is
crucial. A promising minimally invasive oncological treatment called
photodynamic therapy (PDT) involves irradiation of a photosensitizing
drug injected into the vasculature which in turn transfers energy
to the surrounding oxygen, generating heavily cytotoxic reactive oxygen
species (ROS), either directly or indirectly killing the cell. Although
simple in theory, many problems need to be addressed like oxygen waste
and hence resupply, light source delivery to the photosensitizer (PS),
or the cancer cell targeting with the PS. Promising new agents to
tackle multiple issues in PDT are metal nanoclusters (NCs), especially
with gold as the core. They turn out to accumulate well in cancer
cells, be very biocompatible, and even function as PS themselves.
A less common way to surpass the light source delivery problem is
to use X-rays due to low in vivo scattering and absorption cross section,
giving rise to what we will call X-ray photodynamic therapy (X-PDT).
It shows great potential for demolishing cancer cells, prompted by
their high energy. The energy transfer in both cases, PDT and X-PDT,
from PS or NC to oxygen is poorly understood and the subject of current
research. This Tutorial gives an easy to understand introduction to
PDT and X-PDT and their different agents, explains the use of metal
NCs in both heavily related treatment methods, gives an overview of
the known elementary transfer mechanisms between the typical contributors
to PDT and X-PDT, and briefly sketches realized and possible simulation
strategies. It aims to give an understanding of where current research
is lacking and thus what new experiments, theories, and simulations
should be targeted as well as an outlook for possible further theoretical
and computational X-PDT research.