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• A pioneering "grafting from" drug coordination polymerization strategy was proposed. • A fully-coordinated and full-active Cu 2 O/drug core/shell nanoplatform was prepared. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming "immune-cold" tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering "grafting from" drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu 2 O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu 2 O (HA-Cu 2 O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu 2 O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram "immune-cold" tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems. [ABSTRACT FROM AUTHOR]