Engineering nanosystems for ROS-bridged cancer cascade therapy

Developing efficient cancer treatment modalities is crucial, given the tens of thousands of deaths that cancer causes each year. Although there are various treatment modalities available, such as chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), etc., individual treatment approaches have limitations in achieving efficient tumor ablation due to the complex tumor microenvironment and the shortfalls of single therapeutic modality. The recent advancements in material science have led to the emergence of efficient cascade-based nanosystems that optimize these treatment modalities. Among such modalities, cascade therapy triggered by reactive oxygen species (ROS) has proven particularly effective through the synergism between photodynamic and chemodynamic therapies. This review focuses on the recent advances in nanosystem-based synergistic therapy via a cascade of ROS generated by photosensitizers, sonosensitizers, and Fenton reactions, emphasizing the design and cascade therapy mechanism of these approaches. Furthermore, the article covers the challenges and future outlook of such ROS generation-based cascade strategies for cancer therapy.