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. O(2) (.−) produced by the PDT is converted to H(2)O(2) by superoxide dismutase, followed by the transformation of H(2)O(2) to the highly toxic (.)OH via Fenton reactions by Fe(2+) originating from the dissolution of co‐loaded Fe(3)O(4) 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 O(2) (.−) in the presence of nicotinamide adenine dinucleotide phosphate oxidase and thereby improves the treatment efficiency by serving as an additional O(2) (.−) source for production of (.)OH radicals. Improved anticancer efficiency is achieved under both hypoxic and normoxic conditions.