Platelet membrane coating coupled with solar irradiation endows a photodynamic nanosystem with both improved antitumor efficacy and undetectable skin damage

The therapeutic efficacy of tumor photodynamic therapy (PDT) is hindered by the following three challenges. The extremely short lifetime of reactive oxygen species (ROS, the cytotoxic factor of PDT) limits the radius of their action to tens-of-nanometer scale; functionalizing a photodynamic nanosystem with active targeting moieties helps bring the target cells into reach of ROS but requires extra research efforts. Current photodynamic systems are in general excited by light on the short end of near-infrared (NIR) region; deep tissue penetration necessitates the development of those excitable by longer NIR light. Reducing irradiation dose is necessary for avoiding skin damages but impacts the therapeutic outcome; how to resolve this delimma remains a challenge. We herein show that platelet membrane-coating over a photodynamic nanoparticle coupled with solar irradiation may simultaneously resolve all challenges above. Platelet membrane-coating provides both long circulation and active targeting, leading to preferential internalization by tumor over fibroblast cells in vitro and higher tumor uptake than the red blood cell (RBC) membrane-coated counterpart. Preloading a photodynamic sensitizer into a synthetic nanocarrier shifts its absorption peak to longer wavelength, which favors deep tissue penetration. Upon irradiation with NIR light from a solar simulator at extremely low output power density, the platelet membrane-coated photodynamic-nanoparticle outperforms its RBC membrane-coated counterpart and effectively ablates tumor without causing skin damages, which underscores the importance of active targeting in tumor PDT. We anticipate that platelet membrane coating may facilitate the in vivo applications of antitumor photodynamic therapy.