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 (H2O2) which enhances luminol-based chemiluminescence (CL), consequently driving the generation of photochemical singlet oxygen (1O2) 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.
Keywords: anti‐metastasis; chemiexcited phototherapy; nanoreactors; starvation therapy; toehold‐release activation.
© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.