Light-activatable Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles camouflaged Prussian blue nanoparticles for synergistic photothermal and photodynamic therapies of cancer

Multiple therapeutic modalities, such as photodynamic (PDT) and photothermal (PTT) therapies, have been jointly applied to produce a synergistic effect for tumor eradication based on the hyperthermia and generation of reactive oxygen species (ROS) mediated by photoactive agents. Effective delivery of highly efficient photosensitizers and photothermal agents is the key for combination of PDT/PTT. Herein, we propose a strategy to functionalize Prussian blue (PB) nanoparticles (NPs) with Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles. This nanoplatform can address the major issues of these two capable photoactive agents, such as limited biocompatibility, lack of functional chemical groups, and poor bioavailability due to rapid blood clearance or self-aggregation. Specifically, PB NPs were packaged within Ce6-imbedded erythrocyte membrane vesicles, named as PB@RBC/Ce6 NPs, to take advantage of both biological functions of natural erythrocyte membranes and the unique physicochemical properties of synthetic nanoagents. Compared to bare PB NPs or free Ce6, PB@RBC/Ce6 NPs exhibited considerably enhanced cellular uptake and accumulation in tumoral tissues. Moreover, the PB@RBC/Ce6 NP-mediated PDT/PTT combination therapies produced a notable effect in boosting the necrosis and late apoptosis of tumor cells in vitro, and further showed a synergistic therapeutic effect against an orthotopic tumor model in vivo.