Type I Framework Complex: Photocontrolled Superoxide Anion Generator

Photodynamic therapy (PDT) is a clinically approved therapeutic modality that uses photosensitizers (PSs) to generate reactive oxygen species (ROS) upon light irradiation, enabling disease treatment with minimal invasiveness and excellent spatiotemporal precision. Despite these advantages, conventional PDT is fundamentally constrained by the mismatch between its oxygen dependence and the intrinsically hypoxic tumor microenvironment, which markedly compromises therapeutic outcomes. In this context, type I PSs offer a promising solution because they can produce cytotoxic radicals through electron transfer pathways, thereby reducing dependence on oxygen (O₂) and improving efficacy under hypoxic conditions. Organic framework materials have recently emerged as powerful and versatile platforms for constructing type I PSs, owing to their programmable structures, high porosity, and efficient photoinduced charge separation and electron transfer. Importantly, the modular nature of these frameworks enables rational tuning of both structural motifs and compositional building blocks, allowing systematic regulation of light absorption, redox properties, and ROS generation pathways to maximize type I PDT performance. Moreover, organic frameworks can simultaneously function as nanocarriers for therapeutics, facilitating co-delivery and synergistic combinations (e.g., chemotherapy, immunotherapy, or catalytic therapies) that may achieve more durable and comprehensive tumor control. However, current studies remain fragmented, and there is still a lack of an integrated and mechanistically grounded overview that connects framework design principles with type I ROS generation mechanisms and performance optimization strategies. To address this unmet need, this review provides a comprehensive summary of the design strategies, mechanistic insights, and recent progress in organic framework-based type I PSs. We first outline the fundamental principles of type I photochemistry and the key physical and chemical processes underlying type I PDT. We then highlight rational design and modulation strategies to enhance optical properties, promote charge separation, and strengthen oxygen independence. Next, we summarize representative in vivo/in vitro disease models to demonstrate emerging diagnostic and therapeutic applications. Finally, we discuss current challenges and future opportunities for clinical translation, offering practical guidance for the development of next-generation phototherapeutic agents based on these innovative framework systems.