Liquid Nanoparticles for Nanocatalytic Cancer Therapy

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 (Na₂ S₂ O₈ ), 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⁺ /S₂ O₈ ^2- ) after reaching the tumor sites, where the Fe²⁺ further triggers S₂ O₈ ^2- 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.