Calcium peroxide nanoplatform-mediated cancer immunotherapy enhancement: current advances and perspective

The efficacy of cancer immunotherapy is severely constrained by the immunosuppressive tumor microenvironment (ITME), with hypoxia, acidosis, and immune cell dysfunction being key factors contributing to treatment resistance. Calcium peroxide (CaO 2 ) nanomaterials leverage their unique hydrolysis behavior within the acidic tumor microenvironment (TME) to simultaneously release oxygen (O 2 ), hydrogen peroxide (H 2 O 2 ), and calcium ions (Ca 2+ ), while consuming hydrogen ions (H + ). This process synergistically remodels the TME and enhances antitumor immunity through multiple mechanisms: O 2 alleviates hypoxia, thereby reversing immunosuppression and enhancing the efficacy of O 2 -dependent therapies; H 2 O 2 catalyzes the production of highly toxic reactive oxygen species (ROS) via Fenton or Fenton-like reactions, directly killing tumor cells; H + consumption counteracts acidosis and improves immune cell function; and excessive Ca 2+ influx induces calcium (Ca) overload, triggering mitochondrial and endoplasmic reticulum (ER) stress to further amplify apoptosis and immune activation. These effects form a multi-pathway, coordinated immunomodulatory network, offering a novel approach to overcome tumor immune resistance. This review summarizes the strategies and mechanisms of CaO 2 nanoplatforms in cancer immunotherapy, discusses their translational challenges and prospects, and provides insights to advance intelligent nanomedicine for overcoming immunotherapy resistance.