Platelet membrane camouflaged AIEgen-mediated photodynamic therapy improves the effectiveness of anti-PD-L1 immunotherapy in large-burden tumors.

Abstract

Although immunotherapy has achieved recent clinical success in antitumor therapy, it is less effective for solid tumors with large burdens. To overcome this challenge, herein, we report a new strategy based on platelet membrane-camouflaged aggregation-induced emission (AIE) luminogen (Plt-M@P) combined with the anti-programmed death ligand 1 (anti-PD-L1) for tumoral photodynamic-immunotherapy. Plt-M@P is prepared by using poly lactic-co-glycolic acid (PLGA)/PF3-PPh3 complex as a nanocore, and then by co-extrusion with platelet membranes. PF3-PPh3 is an AIE-active conjugated polyelectrolyte with photosensitizing capability for photodynamic therapy (PDT). Plt-M@P exhibits superior tumor targeting capacity in vivo. When applied in small tumor-bearing (~40 mm3) mice, Plt-M@P-mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm3), using Plt-M@P-mediated PDT or anti-PD-L1 alone is less effective, but the combination of both is effective in inhibiting tumor growth. Importantly, this combination therapy has good biocompatibility, as demonstrated by the absence of damage to the major organs, especially the reproductive system. In conclusion, we show that Plt-M@P-mediated PDT can improve anti-PD-L1 immunotherapy by enhancing antitumor effects, providing a promising strategy for the treatment of tumors with large burdens.