Activation of the PD-1/PD-L1 signaling pathway induces T effector (Teff) cells apoptosis in GBM674,675 and is the main driver of the tumor immunosuppressive microenvironment.676–678 In addition, PD-L1 mediates resistance to TMZ in GBM via the AMPK/ULK1 pathway.679 The expression levels of PD-1 and PD-L1 were higher in recurrent GBM than in primary GBM.680 Zhou et al. co-loaded siPD-L1 and TMZ via LPNPs.681 PAsp-g-PEI/dsb was synthesized by grafting PEI onto PAsp via disulfide bonding. Here, SNCA is linked to glioblastoma.