Rui Sang, Biyao Yang, Kainat Zahra, Fei Deng, Zi Gu, Ewa M. Goldys, Wei Deng
Redox dysregulation is a hallmark of numerous pathological conditions, including cancer, chronic inflammatory diseases, fibrosis, neurodegenerative disorders and cardiovascular diseases, where aberrant production of reactive oxygen, nitrogen, sulfur and carbonyl species disrupts cellular signalling, metabolism, immune responses and tissue homeostasis. Despite its central role in disease progression, clinical assessment and therapeutic modulation of redox imbalance remain largely indirect, non-specific, failing to adequately capture the spatially heterogeneous and highly dynamic nature of redox dysregulation. Redox-responsive nanosystems offers the potential to bridge this gap by incorporating redox-sensitive materials that can spatiotemporally sense and respond to disease-associated oxidative or reductive microenvironments. Through predictable chemical or structural transformations triggered by endogenous redox cues, these nanoplatforms enable site-specific imaging, on-demand drug release, catalytic therapy and signal amplification. These capabilities position redox-responsive nanomedicine as a powerful approach for enhancing therapeutic precision while minimising off-target toxicity. This review provides a comprehensive and mechanism-informed overview of redox-responsive nanosystems for advanced drug delivery and precision medicine. We systematically connect disease-associated redox mechanisms with nanoplatform design strategies and functional outcomes across diagnostic, therapeutic and combined theranostic applications. In addition, we critically discuss key translational challenges, including biosafety, pharmacokinetics, large-scale manufacturing and regulatory considerations. Finally, we outline future directions toward clinically translatable, redox-guided nanomedicine. Graphical abstract • Disease-specific redox dysregulation underlies pathological progression and therapy response. • Redox-responsive nanosensors enable spatially resolved monitoring of redox states in vivo . • Redox-activated nanomedicines provide targeted and mechanism-informed therapeutic modulation by selectively responding to pathological redox conditions. • Integrated nanotheranostic platforms couple redox sensing with imaging-guided therapy, enabling coordinated diagnosis and precision intervention. • Redox heterogeneity, biosafety considerations and limited scalability remain key barriers to the clinical translation of redox-based nanomedicines.