Immuno-Nanozymes Mediated Synergistic Chemodynamic/Immuno-Therapy with Potentiated Anti-Tumor Efficacy

Nanozymes mediated chemodynamic therapy (CDT) is a newly developed therapeutic modality with high specificity. The efficacy of CDT, however, still confronts challenges from the immune inhibitory tumor microenvironment (TME). It is thus of great significance to synergize CDT with immunotherapeutic interventions. Herein, this work reports the design and preparation of CpG loaded, Cu²⁺ doped double layered hydroxides nanosheets (CpG/Cu-LDHs) as immuno-nanozymes to potentiate overall anti-tumor efficacy by synergizing CDT with immunogenic cell death (ICD)-activated local and systemic immune responses. Such cooperative CDT-immuno effect together with immunosuppressive TME remodeling capacity conferred by CpG/Cu-LDHs led to effective suppression of both treated primary tumor and untreated distant tumor on a mouse tumor model. Thereby, synergizing CDT with ICD-driven, in situ vaccine-like immunotherapy by immuno-nanozymes provides a novel and generalized paradigm for devising highly efficient and specific anti-tumor strategy without the use of external stimulations.