Enhancing Tumor Photodynamic Synergistic Therapy Efficacy through Generation of Carbon Radicals by Prussian Blue Nanomedicine

Abstract Significant progress has been achieved in tumor therapies utilizing nano-enzymes which could convert hydrogen peroxide into reactive oxygen species (ROS). However, the ROS generated by these enzymes possess a short half-life and exhibit limited diffusion within cells, making it challenging to inflict substantial damage on major organelles for effective tumor therapy. Therefore, it becomes crucial to develop a novel nanoplatform that could extend radicals half-life. Artesunate (ATS) is a Fe (II)-dependent drug, while the limited availability of iron (II), coupled with the poor aqueous solubility of ATS, limits its application. Here, Prussian blue (PB) was selected as a nano-carrier to release Fe (II), thus constructing a hollow Prussian blue/artesunate/methylene blue (HPB/ATS/MB) nanoplatform. HPB degraded and released iron(III), ATS and MB, under the combined effects of NIR irradiation and the unique tumor microenvironment. Moreover, Fe (III) exploited GSH to formation of Fe (II), disturbing the redox homeostasis of tumor cells and Fe (II) reacted with H2O2 and ATS to generate carbon radicals with a long half-life in situ. Furthermore, MB generates 1O2 under laser irradiation conditions. In vitro and in vivo experiments have demonstrated that the HPB/ATS/MB NPs exhibit a synergistic therapeutic effect through photothermal therapy, photodynamic therapy and radical therapy.