Han Wenshuai, Ding Jiayi, Qiao Bo, Yu Yingjie, Sun Hao, Crespy Daniel, Landfester Katharina, Mao Xiangzhao, Jiang Shuai
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, P. R. China.
State Key Laboratory of Marine Food Processing and Safety Control, Ocean University of China, Qingdao, 266404, P. R. China.
Adv Mater. 2025 Mar;37(9):e2415030. doi: 10.1002/adma.202415030. Epub 2025 Jan 10.
Metastasis, the leading cause of mortality in cancer patients, presents challenges for conventional photodynamic therapy (PDT) due to its reliance on localized light and oxygen application to tumors. To overcome these limitations, a self-sustained organelle-mimicking nanoreactor is developed here with programmable DNA switches that enables bio-chem-photocatalytic cascade-driven starvation-photodynamic synergistic therapy against tumor metastasis. Emulating the compartmentalization and positional assembly strategies found in living cells, this nano-organelle reactor allows quantitative co-compartmentalization of multiple functional modules for the designed self-illuminating chemiexcited PDT system. Within the space-confined nanoreactor, biofuel glucose is converted to hydrogen peroxide (HO) which enhances luminol-based chemiluminescence (CL), consequently driving the generation of photochemical singlet oxygen (O) via chemiluminescence resonance energy transfer. Meanwhile, hemoglobin functions as a synchronized oxygen supplier for both glucose oxidation and PDT, while also exhibiting peroxidase-like activity to produce hydroxyl radicals (·OH). Crucially, the nanoreactor keeps switching off in normal tissues, with on-demand activation in tumors through toehold-mediated strand displacement. These findings demonstrate that this nanoreactor, which is self-sufficient in light and oxygen and precise in striking tumors, presents a promising paradigm for managing highly metastatic cancers.
转移是癌症患者死亡的主要原因，由于传统光动力疗法（PDT）依赖于对肿瘤进行局部光照和供氧，因此在治疗转移方面面临挑战。为了克服这些局限性，本文开发了一种具有可编程DNA开关的自持细胞器模拟纳米反应器，该反应器能够实现生物 - 化学 - 光催化级联驱动的饥饿 - 光动力协同治疗肿瘤转移。该纳米细胞器反应器模仿活细胞中的区室化和位置组装策略，允许将多个功能模块定量共区室化，用于设计的自发光化学激发光动力疗法系统。在空间受限的纳米反应器内，生物燃料葡萄糖被转化为过氧化氢（H₂O₂），其增强了基于鲁米诺的化学发光（CL），从而通过化学发光共振能量转移驱动光化学单线态氧（¹O₂）的产生。同时，血红蛋白作为葡萄糖氧化和光动力疗法的同步氧供体，还表现出过氧化物酶样活性以产生羟基自由基（·OH）。至关重要的是，纳米反应器在正常组织中保持关闭状态，通过引发链置换在肿瘤中实现按需激活。这些发现表明，这种纳米反应器在光和氧方面自给自足且能精确靶向肿瘤，为治疗高转移性癌症提供了一个有前景的范例。
