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State-matched redox nanomedicine for cell fate control and multicompartment therapeutic windows
Jiacheng Li1, Jiazhen Liu2, Jia Cai3
1Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; Nuclear Physics and Medical Research Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Tumors persist under sustained redox stress by coupling increased reactive-species production to antioxidant buffering, metabolic plasticity and multicellular support. This creates therapeutic vulnerabilities whose tractability depends on the biological state of the exposed compartment. Here, we frame redox nanomedicine as state-matched manipulation of oxidant flux, antioxidant buffering, oxygen and substrate availability, localization, duration and spatial coverage. We propose that therapeutic outcome emerges from chemistry, exposure and the presence of an executable redox dependency together with the machinery required for adaptation, apoptosis, ferroptosis, pyroptosis or cuproptosis. Redox perturbations also propagate through immune, vascular, stromal and metabolic compartments, generating both therapeutic benefits and liabilities. We therefore integrate redox-state dependence, cell-fate assignment, multicompartment effects and translational target engagement into a unified framework. A state-matched development strategy begins with a defined biological dependency, measures local exposure and target engagement, and uses pharmacokinetic, safety and biomarker data to refine product design and patient selection. This framework positions redox nanomedicine as mechanistically testable control of tumor redox states within a defined therapeutic window.
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