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.

以下三个挑战阻碍了肿瘤光动力疗法（PDT）的治疗功效。活性氧（ROS，PDT的细胞毒性因子）的寿命极短，将它们的作用半径限制在几十纳米的范围内。具有主动靶向部分的光动力学纳米系统功能化有助于将靶细胞带入ROS，但需要额外的研究工作。当前的光动力系统通常在近红外（NIR）区域的短端被光激发。较深的组织穿透需要通过更长的近红外光激发那些被激发的细胞。减少辐照剂量对于避免皮肤损害是必要的，但是会影响治疗效果。如何解决这一问题仍然是一个挑战。我们在本文中显示在光动力纳米颗粒上与太阳辐射结合的血小板膜包衣可以同时解决上述所有挑战。血小板膜包衣提供长循环和主动靶向作用，导致肿瘤在体外比成纤维细胞优先发生内在化，并且比红细胞（RBC）膜包被的肿瘤具有更高的肿瘤吸收率。将光动力敏化剂预装到合成纳米载体中，会将其吸收峰移至更长的波长，这有利于深层组织的渗透。在太阳模拟器上以极低的输出功率密度照射NIR光时，血小板膜涂层的光动力纳米粒子的性能优于其RBC膜涂层的纳米粒子，并在不引起皮肤损害的情况下有效消融肿瘤，这强调了在肿瘤PDT中主动靶向的重要性。我们预期血小板膜包衣可以促进抗肿瘤光动力疗法的体内应用。