For brain tumors, blood exosomes co-delivering cytoplasmic phospholipase A2 (cPLA2) siRNA and metformin crossed the BBB and reprogrammed glioblastoma energy metabolism in patient-derived xenograft (PDX) models, prolonging survival and enabling biomarker-guided personalization via polymerase 1 and transcript release factor (PTRF)-mediated uptake [71]; macrophage exosomes co-loaded with panobinostat and mutation of p53-induced protein phosphatase 1(PPM1D) siRNA similarly achieved BBB transit and extended survival in diffuse intrinsic pontine gliomas (DIPG) [72]. The gene discussed is TP53; the disease is diffuse intrinsic pontine glioma.