Rostyslav Marunych, Dorota Bartusik-Aebisher, Barbara Smolak, Klaudia Dynarowicz, David Aebisher
This review analyzes how Zinc(II) coordination alters the electronic configuration of porphyrin-based photosensitizers to optimize reactive oxygen species (ROS) generation and subcellular targeting in photodynamic therapy (PDT). By focusing on the structural design principles that govern excited-state behavior, the work moves beyond clinical descriptions to provide a mechanistic understanding of how engineered metalloporphyrins can achieve precise tumor destruction. When these engineered metal porphyrins are exposed to specific wavelengths of light, they transfer energy to create ROS, such as singlet oxygen, which directly damages and kills tumor tissue. The review evaluates structural modifications that drive selective accumulation within critical subcellular organelles, notably the mitochondria, to maximize cytotoxic efficiency. By analyzing the impact of the tumor microenvironment on hypoxia, the work outlines strategies for maintaining efficacy in oxygen-deprived zones and highlights how the biocompatible, redox-inactive nature of Zinc(II) minimizes systemic toxicity, providing a blueprint for the design of targeted, translation-ready photosensitizers.