Scheme 1.
PD-L1 multivalent binding of ICB-LPs+UV for effective immune checkpoint blockade therapy. (A) The ICB-LPs are prepared by formulation of DC8,9PC, DPPC and anti-PD-L1-DSPE-PEG2k, which can promote intermolecular crosslinking within the liposomal bilayers upon UV irradiation. (B) ICB-LPs+UV highly accumulates within the tumor tissues via EPR effect and PD-L1 receptor-mediated active targeting mechanisms. (C) ICB-LPs+UV efficiently promotes multivalent binding with the PD-L1 on the tumor cell surface, which efficiently internalizes in the cells via nanoparticle-derived endocytosis with aim to deliver PD-L1 to the lysosomes. As a result of effective lysosomal PD-L1 degradation, a potent CTL-mediated antitumor immunity is induced. (D) In contrast, PD-L1 mAb-induced PD-L1 blockade prone to be recycled back to the membranes because of their intrinsic endocytosis pathway targeting recycling endosomes, thereby reducing CTL activity.