Hollow MnO₂-based multifunctional nanoplatform for enhanced tumor chemodynamic therapy

The inherent tumor microenvironment (TME) of hypoxia and high glutathione (GSH) hinders the production of reactive oxygen species (ROS), yet which are crucial roles to make the oxygen-independent chemodynamic therapy (CDT) outstanding. Herein, we constructed hyaluronic acid (HA)-modified and peroxymonosulfate (PMS)-loaded hollow manganese dioxide (HMn) nanoparticles for not only TME-response drug release but also the distinct ROS donors to strengthen CDT. Upon enriched in the tumor site, the prepared nanotheranostic agent (HA@HMn/PMS) depleted local GSH to reduce MnO₂ to Mn²⁺, followed by generating •OH and •SO₄⁻ through Fenton-like reaction and activation of PMS, respectively. The bring in of •SO₄⁻, a rare radical possessing exceptional oxidizing ability and oxygen-independent property, breaks the limitations of traditional ROS and causes serious damage to tumor cells. In a xenograft mouse tumor model, detailed studies demonstrated that HA@HMn/PMS can significantly inhibit tumor growth. This work inspires the enormous potential of CDT in investigating the application of multifunctional nanosystems by combining the consumption of GSH and the synergistic effect of multiple radicals in oncotherapy.