Synergistic Anticancer Therapy by Ovalbumin Encapsulation-Enabled Tandem Reactive Oxygen Species Generation

The anticancer efficacy of photodynamic therapy (PDT) is limited due to the hypoxic features of solid tumors. We report synergistic PDT/chemotherapy with integrated tandem Fenton reactions mediated by ovalbumin encapsulation for improved in vivo anticancer therapy via an enhanced reactive oxygen species (ROS) generation mechanism. O₂^.− produced by the PDT is converted to H₂O₂ by superoxide dismutase, followed by the transformation of H₂O₂ to the highly toxic ^.OH via Fenton reactions by Fe²⁺ originating from the dissolution of co-loaded Fe₃O₄ nanoparticles. The PDT process further facilitates the endosomal/lysosomal escape of the active agents and enhances their intracellular delivery to the nucleus—even for drug-resistant cells. Cisplatin generates O₂^.− in the presence of nicotinamide adenine dinucleotide phosphate oxidase and thereby improves the treatment efficiency by serving as an additional O₂^.− source for production of ^.OH radicals. Improved anticancer efficiency is achieved under both hypoxic and normoxic conditions.