Liquid Nanoparticles for Nanocatalytic Cancer Therapy

Abstract Nanotechnology is revolutionizing cancer therapy, and catalyzes the emerging of ion‐involved cancer‐therapeutic modality, which unfortunately suffers from undesirable nanocarriers for efficient intracellular ion delivery. To radically extricate from this critical issue, the glutathione (GSH)‐responsive organosilica network is employed to lock the liquid drops at the nanoscale via a general bottom‐up strategy to achieve the systemic delivery of “ion drugs”. In this work, a sulfate radical generation donor (Na₂S₂O₈), as a paradigm “ion drug”, is entrapped into this liquid nanoparticle for efficiently delivering to the tumor region. After further surface engineering with pH‐responsive tannic acid‐Fe²⁺ framework, these liquid nanoparticles achieve tumor‐microenvironmental pH/GSH‐dual responsive ion release (Fe²⁺/Na⁺/S₂O₈²⁻) after reaching the tumor sites, where the Fe²⁺ further triggers S₂O₈²⁻ to generate toxic •SO₄⁻ and •OH, effectively executing cancer cell ferroptosis (Fe²⁺, reactive oxygen species—ROS) and pyroptosis (Na⁺, ROS). Such a tumor‐responsive/specific liquid nanoplatform is highly instructive for further ion‐mediated nanomedicine and disease treatment.