Nanomedicine-powered redox homeostasis modulation: Disrupting antioxidant systems and inducing oxidative stress for...

Precise regulation of cellular redox balance is fundamental for maintaining normal physiological function and overall homeostasis. Oxidative stress arises when reactive oxygen species (ROS) overwhelm cellular antioxidant defenses, disrupting redox equilibrium. It plays a pivotal role in tumor initiation, progression, and metastasis. Tumor cells maintain remarkably elevated levels of both oxidants and antioxidants compared with normal cells, resulting in a dysregulated redox homeostasis that is particularly vulnerable to oxidative stress induced by exogenous stimuli. A growing body of evidence suggests that deliberate modulation of redox homeostasis through inducing intracellular ROS burst and disrupting antioxidant defense systems to enhance oxidative stress, represents a promising therapeutic strategy for precision tumor therapy. To date, various nanoparticles have been found to disrupt redox balance based on their catalytic activity, biological regulatory functions, and drug-delivery capabilities. In this review, we systematically overview oxidative and antioxidant systems in tumor cells and summarize recent advances in nanomedicine-based strategies for redox homeostasis modulation, with an emphasis on the regulation of metabolites, enzyme activities, and signaling pathways. Moreover, we evaluate current challenges and propose actionable strategies to promote clinical translation. By integrating mechanistic understanding with rational nanodrugs design, this review aims to support the development of redox-targeted therapeutic approaches and promote their future implementation in precision tumor therapy.