Zhao Yingming, Li Shubin, Liu Yanhao, Li Chao, Zhao Jingjing, Ren Yongshuo, Zhao Wan, Zhang Xiangxiang, Cui Xinyu, Tang Xuefeng, Ren Peipei, Han Xiaojun
State Key Laboratory of Urban Water Resource and Environment, MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, No. 92, West Da-Zhi Street, Harbin, 150001, China.
Adv Mater. 2025 Jul;37(28):e2500242. doi: 10.1002/adma.202500242. Epub 2025 May 6.
Membraneless organelles (MLOs) formed by liquid-liquid phase separation exhibit diverse important biofunctions in cells. The construction of artificial cells containing MLOs with enhanced complexity and functions is still challenging. Here a light-responsive protein, Cry2olig-IDRs, is designed and purified to form MLOs upon light (488 nm) irradiation. They are capable of rapidly recruiting positively charged inducible nitric oxide synthase (iNOS) from surroundings to regulate its activity for NO production. NO-artificial cells are constructed by encapsulating Cry2olig-IDRs and iNOS into giant unilamellar vesicles, which are capable of rapid production of NO with high concentration due to the formation of MLOs upon light irradiation. NO-artificial cells are confirmed to possess the ability for melanoma tumor therapy in mice. These findings provide an efficient method for remotely regulating enzyme activity inside artificial cells, paving the path to build more sophisticated artificial cells for their biomedical applications.
通过液-液相分离形成的无膜细胞器（MLOs）在细胞中展现出多种重要的生物功能。构建具有更高复杂性和功能的含MLOs人工细胞仍然具有挑战性。在此，设计并纯化了一种光响应蛋白Cry2olig-IDRs，其在光（488 nm）照射下形成MLOs。它们能够迅速从周围环境中招募带正电荷的诱导型一氧化氮合酶（iNOS），以调节其产生NO的活性。通过将Cry2olig-IDRs和iNOS封装到巨型单层囊泡中构建了NO人工细胞，该细胞在光照射下由于形成MLOs而能够快速产生高浓度的NO。经证实，NO人工细胞具有对小鼠黑色素瘤肿瘤进行治疗的能力。这些发现为远程调节人工细胞内的酶活性提供了一种有效方法，为构建更复杂的人工细胞用于生物医学应用铺平了道路。
