Dual-Defect Nitrogen-Rich Carbon Nitride-Based Heterostructural Nanocatalyst for Improving the Therapeutic Efficacy of αPD-1 via Tumor Immune Microenvironment Remodelling

Abstract

Low immunogenicity, insufficient immune infiltrates, and inhibitive microenvironment of tumors ruthlessly weakened the therapeutic efficacy of immunotherapies. How to improve the therapy efficacy by reshaping the tumor immune microenvironment still remains a challenge that needs to be urgently addressed. Here, a novel dual-defect nitrogen-rich carbon nitride-based heterostructural nanocatalyst (CNO@CuMS) possessing brilliant piezocatalytic H₂O₂ generation, sonocatalytic ¹O₂ generation, Fenton-like catalytic •OH generation, and cell cuproptosis inducing properties are developed. Accompanied by the ultrasonic treatment, immunogenic cell death (ICD) and the subsequent releasing of damage-associated molecular patterns (DAMPs) of tumor cells are successfully triggered by CNO@CuMS, which resulted in the activation of systematic antitumor response and enhanced the infiltration of CD8⁺ cytotoxic T lymphocytes and natural killer (NK) cells at tumor site. The large quantitatively generated reactive oxygen species (ROS) also promoted the polarization of M2-type macrophage to M1-type as well. Benefitting from this tumor immune microenvironment remodelling effect, remarkable malignant orthotopic osteosarcoma therapy efficacy is achieved employing CNO@CuMS + αPD-1 combination strategy under ultrasonic treatment, with no significant side effects are observed. This research not only proposes a method to fabricate high proformance carbon nitride-based nanocatalyst but also provides a new strategy to realize highly efficient malignant bone tumor therapy during clinical practice.