Palladium-based metal–organic coordination nanoparticles for efficient tumor treatment via synergistic enhancement of ROS production

The potential therapeutic benefits of reactive oxygen species (ROS) have garnered significant interest in the field of anti-tumor research. Chemodynamic therapy (CDT) serves as a common method for the treatment of tumors, and it employs Fenton/Fenton-like reactions to transform hydrogen peroxide (H 2 O 2 ) into highly cytotoxic ROS. However, the single treatment mode, relatively low catalytic efficiency of CDT reagents, and insufficient endogenous H 2 O 2 production limit its anti-tumor activity. To address these issues and inspired by the concept of metal-coordinated nanomedicine, we designed and prepared multifunctional palladium-based nanoparticles (Pd@RB@LAP NPs). The nanoparticles were synthesized by coordinating palladium ions (Pd 2+ ) with Rose Bengal (RB) and subsequent loading of β-lapachone (LAP). LAP could produce a large amount of H 2 O 2 through the quinone–hydroquinone–quinone redox cycle catalyzed by the NQO1 enzyme [NAD(P)H: quinone oxidoreductase 1] overexpressed at the tumor site. Pd 2+ acted as a catalyst which could convert H 2 O 2 into hydroxyl radical ˙OH, and RB as a photosensitizer under light illumination could also generate ROS ( 1 O 2 ). The oxidative stress created by the excess ROS could increase the NOQ1 level and further promote ROS generation, thus a positive feedback loop was created. Both in vitro and in vivo experiments provide clear evidence of the outstanding CDT efficiency and tumor growth suppression achieved by the Pd@RB@LAP NPs. This nanoplatform offers a simple but efficient paradigm for ROS-mediated tumor therapy.