Cascade Catalytic Nanoplatform Based on "Butterfly Effect" for Enhanced Immunotherapy.

The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP-GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H2 O2 , which not only realizes tumor starvation therapy, but also provides H2 O2 for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe2+ and Fe3+ ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe2+ and further generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP-GOD@ART manipulates TME characteristics and leads to "butterfly effect", which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1-TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP-GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.

US-triggered ultra-sensitive "thrombus constructor" for precise tumor therapy.

Embolization therapy is an attractive strategy for antitumor therapy, especially for solid tumors. In vivo self-coagulation behavior holds great potential in a new type of tumor embolization therapy. However, spatiotemporal controllable in situ formation of thrombus in tumor is a challenge. Herein, an ultrasound (US)-responsive ultra-sensitive "thrombus constructor" (UUNC), which was prepared by loading thrombin into a nanobubble, and modified with NGR peptide on its surface, is rational designed for tumor embolization therapy. Benefiting from the targeting ability of NGR peptides to tumor neovascularization, UUNC efficiently enriched in tumor vessels, and then released thrombin rapidly to form thrombi in situ of tumor blood vessels in the presence of US. In vivo antitumor experiments demonstrated that UUNC could significantly lead to tumor cell apoptosis and necrosis, and the tumor growth inhibition rate (TGI) was 85.3% with a transient US in tumor, while maintain high stability, and no obvious thrombus was observed in normal tissues. UUNC holds an attractive potential for tumor embolization therapy via spatiotemporal controllable thrombus construct strategy.