Palladium-based metal-organic coordination nanoparticles for efficient tumor treatment 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 &z.rad;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. Multifunctional palladium-based metal-organic coordination nanoparticles (Pd@RB@LAP NPs) are designed for synergistic ROS-mediated tumor therapy.