Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Abstract Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials‐based approaches involving modulating intra‐ or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.