Nanoparticles Selectively Regulate the Generation and Scavenging of Multiple Reactive Oxygen Species at Designated Locations and States

Photodynamic therapy (PDT) is recognized as a promising therapeutic modality for cancer, psoriasis, bacterial infection, atherosclerosis, and other diseases, yet confronts persistent challenges of oxygen dependency, limited diversity of reactive oxygen species (ROS), and collateral photodamage to healthy tissues. Here, we report that unlike traditional PDT, near-infrared-activated Prussian blue nanoparticles (PBs) uniquely interact with hydrogen peroxide (H 2 O 2 ) to concurrently generate hydroxyl radicals (·OH), hydroperoxyl radicals (·OOH), and singlet oxygen ( 1 O 2 ) through an oxygen-independent pathway, thereby compensating for the damage and selectivity differences between distinct ROS. PB, H 2 O 2, and light are the three essential factors for producing ROS. Furthermore, PBs exhibit the ability to scavenge H 2 O 2, ·OH, and ·OOH, thereby maintaining the redox homeostasis and showing negligible phototoxicity in normal tissues. Intriguingly, light irradiation enables PBs to selectively regulate both generation and scavenging of ROS. PB shows a powerful capability to selectively regulate the generation and scavenging of ROS at the designated location and time. Proof-of-concept validation through an infected wound murine model reveals that PBs’ exceptional therapeutic efficacy, achieving unprecedented healing outcomes. The discovery of PB as a special photosensitizer holds promise for enriching the fundamental understanding of PDT, overcoming its inherent limitations, and advancing the development of next-generation PDT strategies.