Metal-based nanoparticles in cancer therapy: Exploring photodynamic therapy and its interplay with regulated cell death pathways

Photodynamic therapy (PDT) represents a non-invasive treatment strategy currently utilized in the clinical management of selected cancers and infections. This technique is predicated on the administration of a photosensitizer (PS) and subsequent irradiation with light of specific wavelengths, thereby generating reactive oxygen species (ROS) within targeted cells. The cellular effects of PDT are dependent on both the localization of the PS and the severity of ROS challenge, potentially leading to the stimulation of various cell death modalities. For many years, the concept of regulated cell death (RCD) triggered by photodynamic reactions predominantly encompassed apoptosis, necrosis, and autophagy. However, in recent decades, further explorations have unveiled additional cell death modalities, such as necroptosis, ferroptosis, cuproptosis, pyroptosis, parthanatos, and immunogenic cell death (ICD), which helps to achieve tumor cell elimination. Recently, nanoparticles (NPs) have demonstrated substantial advantages over traditional PSs and become important components of PDT, due to their improved physicochemical properties, such as enhanced solubility and superior specificity for targeted cells. This review aims to summarize recent advancements in the applications of different metal-based NPs as PSs or delivery systems for optimized PDT in cancer treatment. Furthermore, it mechanistically highlights the contribution of RCD pathways during PDT with metal NPs and how these forms of cell death can improve specific PDT regimens in cancer therapy.