KMnO ₄ ‐Laden Hollow Nanoformulations Induce an Oxidative Stress Storm for Cascade Therapy of Tumors

Abstract Delivering highly reactive species that can break the high level of redox homeostasis and cause irreversible death to cancer cells is a potential anticancer treatment strategy, which still remains a challenge due to the inevitable leakage and dissipation during the process of delivery. In this work, a radical generation donor (KMnO 4 ) inhabited manganese dioxide (MnO 2 ) nano‐formulation (KM) is constructed for cancer therapy. This study has found that the laden KMnO 4 steadily remains inside MnO 2 and does not diffuse out within 100 days of the experiment. To avoid the depletion of KMnO 4 , tetradecanol (Td), a phase transition material, is applied to fill the KM (KMTd), and followed by coating cytomembrane to form the nanosystem (KMTdM). After homologous targeted gathering at tumor sites, the housed Td is melted under near‐infrared irradiation, and the KMnO 4 is liberated to magnify the oxidative damage caused by MnO 2 ‐mediated glutathione depletion, resulting in cascade oxidative damage and death to cancer cells. This work not only provides a paradigm of delivering KMnO 4 for cancer cascade therapy, but also broadens application scenarios for conventional drugs.