Schematic illustration of PIH-NO for cancer therapy and immune activation. PIH-NO was constructed by IR780 and HSA-NO with oxygen saturation. After intravenous injection, it could increase blood perfusion, increase EPR effect and relive hypoxia. It could prefer to accumulate in mitochondria. After with ultrasound irradiation, it could release oxygen and NO to enhance SDT, and damage mitochondria, which induce immunogenic cell death to promote DC maturation. The generation NO and RNS could polarize M2 macrophages to M1 phenotype and reduce MDSC to reverse immunosuppression microenvironment. All these approaches increase CD8+ T cells infiltration to inhibit primary tumor and lung metastasis.