Magnetically Boosted Generation of Intracellular Reactive Oxygen Species toward Magneto-Photodynamic Therapy

The generation of reactive oxygen species (ROS) in photodynamic therapy (PDT) involves excited-state intermediates with both singlet and triplet spin configurations, which provides possibilities to modulate the ROS production in PDT under an external magnetic field. Here, we present that magnetically modulated ROS production can promote PDT efficacy and develop a magnetic-field-assisted PDT (magneto-PDT) method for effectively and selectively killing cancer cells. The photosensitization reaction between excited-state riboflavin and oxygen molecules is influenced by the applied field, and the overall magnetic field effect (MFE) shows a moderate increase at a low field (<1000 G) and then a boost up to the saturation ∼100% at a high field (>1000 G). It is found that the spin precession occurring in radical ion pairs (electron transfer from riboflavin to oxygen) facilitates the O₂^•- generation at the low field. In comparison, the spin splitting in an encounter complex (energy transfer from riboflavin to oxygen) benefits the production of ¹O₂ species at the high field. The field modulation on the two types of ROS in PDT, i.e., O₂^•- and ¹O₂, is also demonstrated in living cells. The magneto-PDT strategy shows the capability to inhibit the proliferation of cancer cells (e.g., HeLa, RBL-2H3, and MCF-7) effectively and selectively, which reveals the potential of using the MFE on chemical reactions in biological applications.