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

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.