Delivery of Mitoxantrone by Biodegradable Cobalt‐Doped Hollow Prussian Blue Nanoparticles for Synergetic Photothermal Amplified Chemodynamic Therapy/Chemotherapy/Metalloimmunotherapy Against Tumor

ABSTRACT

Immunotherapy has revolutionized antitumor treatment, but its effectiveness is severely compromised by the immunosuppressive tumor microenvironment (TME) and inadequate induction of antitumor immune responses, with most solid tumors remaining immunologically “cold” and unresponsive to monotherapies. Mitoxantrone (MTO), a first‐line chemotherapeutic agent, is additionally limited by poor bioavailability, acquired drug resistance, and insufficient immune activation. Herein, we developed biodegradable cobalt‐doped hollow Prussian blue nanoparticles loaded with MTO (CHPB‐MTO) as a multifunctional nanoplatform for synergistic tumor therapy integrating chemotherapy, photothermal‐enhanced chemodynamic therapy, and metalloimmunotherapy. CHPB‐MTO displayed high photothermal conversion efficiency and catalytic activity, triggering photothermally driven reactive oxygen species generation. The acidic TME accelerates the degradation of CHPB‐MTO and the release of MTO, and the process is further promoted by local photothermal effects. Oxidative injury combined with MTO chemotherapy caused pronounced DNA damage, thereby activating the cGAS‐STING pathway. Cobalt ions released from degraded CHPB further amplify cGAS‐STING signaling. Consequently, CHPB‐MTO promoted immunogenic cell death and systemic antitumor immunity, resulting in the inhibition of tumor growth, metastasis, and recurrence, with no discernible systemic toxicity owing to its biodegradability. Collectively, this multifunctional CHPB‐MTO nanoplatform integrates synergistic therapy and imaging functions, highlighting great potential as a novel synergistic strategy for metastatic tumor treatment.