Platelet membrane camouflaged <scp>AIEgen</scp> ‐mediated photodynamic therapy improves the effectiveness of <scp>anti‐PD‐L1</scp> immunotherapy in large‐burden tumors
Jun Dai, Meng Wu, Yating Xu, Hongming Yao, Xiaoding Lou, Yuning Hong, Jian Zhou, Fan Xia, Shixuan Wang
Abstract
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‐PPh 3 complex as a nanocore, and then by co‐extrusion with platelet membranes. PF3‐PPh 3 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 mm 3 ) mice, Plt‐M@P‐mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm 3 ), 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.