Fig. 1. Schematic illustration of cRGD- mix Man-pRNC_{Thioether+DEA}@R848 mediated in situ tumor vaccination and TAMs polarization with nanocarrier itself as the tumor ICD inducer.

cRGD-pRNC_{Thioether+DEA} selectively targeting B16F10 tumor induces metabolism regulation with oxidative phosphorylation elevation and activates GSDMD with pyroptosis for tumor ICD. After combination with R848, cRGD-pRNC_{Thioether+DEA}@R848 forms in situ tumor vaccination. Man-pRNC_{Thioether+DEA}@R848 specifically targets TAMs leading to polarization into M1 phenotype with iNOS, CD80 expression and IL-12 secretion increment. After combination with anti-PD-1 and anti-CD47, the mixed nanoformulation elicits antitumor immune response with Treg decrement and CD8⁺/CD4⁺ T cell proliferation increment.