Photodynamic therapy (PDT) utilizes photosensitizers (PSs) to produce reactive oxygen species (ROSs) upon irradiation, which causes the shutdown of vessels and deprives the tumor of nutrients and oxygen, and in turn induces adverse effects on the immune system. However, significant efforts are needed to increase the efficiency in PDT in terms of light delivery to specific PSs for the clinical treatment of tumors located deep under the skin. Even though PDT offers a disease site-specific treatment modality, current efforts are directed to improve the solubility (in body fluids and injectable solvents), photostability, amphiphilicity (for tissue penetration), elimination, and systemic toxicity of traditional PSs based on porphyrin derivatives. Nanostructured materials show promising features to achieve most of such combined efforts. They can be artificially engineered to carry multiple theranostic agents onto targeted tumor sites. However, recent studies on photosensitive Cd-based nanostructures, mostly used in PDT, indicate that leeching of Cd2+ ions is stimulated when they are exposed to harsh biological conditions for continuous periods of time, thus making them acutely toxic and hindering their applications in in vivo settings. Since nanostructured materials are not completely immune to degradation, great strides have been made to seek new alternatives. In this review, we focus on the latest advances of Cd-free nanostructured metal transition sulfides (MTSs) as alternative PSs and study their high-energy transfer efficiency, rational designs, and potential applications in cancer-targeted PDT. Nanostructured MTSs are discussed in the context of their versatility to serve as phototherapy agents and superior properties, including their strong absorption in the NIR region, excellent photothermal conversion efficiency, controlled reactive oxygen species (ROS) production, versatile surface chemistry, high fluorescence, and structural and thermal stability. We discuss the latest advancements in correlating the self-aggregation of MTSs with their passive tumor cell targeting, highlighting their ability to efficiently produce ROSs, and mitigating their dark toxicity through polymeric functionalization. Treatment of deep-seated tumors by using these PSs upon preferential uptake by tumor tissues (due to the enhanced permeability and retention effect) is also reviewed. We finally summarize the main future perspectives of MTSs as next-generation PSs within the context of cancer theranostics. Graphical Abstract

No abstract