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光动力疗法通过在肿瘤部位注射或外敷光敏药物，随后光照产生光动力效应和大量氧自由基，从而将肿瘤细胞或组织杀死，是手术、放疗、化疗之外的又一种靶向疗法，其最大优点是选择性破坏肿瘤组织、对正常组织损伤小、治疗针对性强。不过，由于光敏药物难以降解、光穿透力和设备的局限性，光动力疗法尚未被广泛用于癌症治疗。 2020年9月11日，美国科学促进会《科学》旗下《科学进展》发表韩国汉阳大学、韩国基础科学研究院、蔚山大学首尔峨山医院的研究报告，利用针对乳腺癌的自发光蛋白质，研发了一种生物荧光诱导型蛋白质光动力疗法。 萤光素酶是自然界中能够催化荧光素产生荧光的酶，主要来自萤火虫或细菌。该研究将萤光素酶与能够生成氧自由基的蛋白质进行结合，该蛋白质可自发光且可降解。 腔肠素是一种存在于水母等水生腔肠动物体内的萤光素。将萤光素酶与氧自由基生成蛋白质暴露于腔肠素，即使没有外来光线照射，也可在细胞膜中产生生物荧光敏感型氧自由基，与前导肽融合而引起多种乳腺癌细胞死亡，包括激素受体阳性乳腺癌细胞MCF-7、起源于黑色素瘤的乳腺癌细胞MDA-MB-435、三阴性乳腺癌细胞MDA-MB-231。 萤光生成反应非常节省能量，几乎全部能量都被转化为光，与之形成鲜明对比的是白炽灯，大约仅10%的能量被转化为光，剩余的能量都变为热能而被浪费。即使光能极低，生物荧光诱导型蛋白质光动力疗法对患者原发乳腺癌细胞和体内肿瘤异种移植小鼠模型也具有靶向治疗作用。 因此，该研究结果表明，生物荧光诱导型蛋白质光动力疗法有望被用于三阴性乳腺癌等多种癌症的靶向治疗，故有必要进一步开展临床研究进行验证。 Sci Adv. 2020 Sep 11;6(37):eaba3009. Self-luminescent photodynamic therapy using breast cancer targeted proteins. Eun Hye Kim, Sangwoo Park, Yun Kyu Kim, Minwoo Moon, Jeongwon Park, Kyung Jin Lee, Seongsoo Lee, Young-Pil Kim. Hanyang University, Seoul, Korea; Korea Basic Science Institute, Gwangju, Korea; University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. 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. DOI: 10.1126/sciadv.aba3009
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