Nanospiky Copper Peroxide as Lactate-Modulating Nanoadjuvant To Induce Cuproptosis and Pyroptosis for Enhanced Tumor Immunotherapy.

Abstract

Constructing new types of nanomaterials to enhance antigen presentation and simultaneously reverse the immunosuppressive tumor microenvironment (TME) is crucial to improving the therapeutic effect of tumor immunotherapy. Herein, nanospiky copper peroxide nanoadjuvant has been produced via a straightforward ion substitution process between Cu²⁺ and calcium carbonate nanoparticles in water followed by reaction with hydrogen peroxide, then loaded with the lactate metabolism regulator fluvastatin sodium and modified with the tumor-targeting molecule hyaluronic acid (defined as NSCuO₂@F@HA). The obtained NSCuO₂@F@HA nanoparticles not only regulate lactate metabolism by suppressing the extracellular efflux of lactic acid to reverse the immunosuppressive TME but also increase the content of Cu²⁺ and reactive oxygen species within tumor cells to effectively induce cuproptosis and pyroptosis of tumor cells, further enhancing the presentation of tumor-associated antigens. In consequence, NSCuO₂ nanoparticles will offer a powerful reference for nanomaterials serving as therapeutic nanoadjuvants to enhance the efficacy of antitumor immunotherapy.