SPNs improve tumor penetration and remodel the tumor microenvironment by degrading hyaluronic acid. Under sound activation, they generate singlet oxygen for SDT, induce ICD, and trigger the controlled release of R848 and NLG919, activating dendritic cells and inhibiting IDO, resulting in a powerful anti-tumor immune response that almost completely suppresses tumor growth and inhibits metastasis. Here, IDO1 is linked to neoplasm.