Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)–induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)–generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to coelenterazine-h as a substrate for luciferase without external light irradiation, Luc-RGP fused with a small lead peptide–induced breast cancer cell death through the generation of BL-sensitive ROS in the plasma membrane. Even with extremely low light energy, BLiP-PDT exhibited targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BLiP-PDT is immediately useful as a promising theranostic approach against various cancers.

尽管光动力疗法（PDT）具有潜力，但由于光敏药物不可降解的风险以及光穿透和仪器的限制，其在癌症治疗中的全面应用尚未实现。在这里，我们通过荧光素酶和活性氧（ROS）生成蛋白（Luc-RGP）的结合，提出了生物发光（BL）诱导的蛋白质PDT（BLiP-PDT），该蛋白是自发光且可降解的。在没有外部光照射的情况下，暴露于作为荧光素酶底物的腔肠素-h后，Luc-RGP与一种小铅肽融合，通过在质膜中产生BL敏感的ROS来诱导乳腺癌细胞死亡。即使在极低的光能下，BLiP-PDT 对患者的原发性乳腺癌细胞和体内肿瘤异种移植小鼠模型也表现出靶向作用。这些发现表明，BLiP-PDT 作为一种有前途的治疗各种癌症的治疗方法立即有用。