Oxidative Stress-Guided Gold Nanoparticles for Cancer Theranostics

Gold nanoparticles offer a versatile platform for cancer theranostics because their high atomic number can enhance X-ray energy deposition, their plasmonic properties support photothermal and photoacoustic applications, and their surfaces allow drug loading and molecular targeting. However, therapeutic benefit remains heterogeneous because tumor uptake, intratumoral coverage, and subcellular localization determine whether deposited gold can be converted into biologically effective damage. Redox context further shapes this conversion by determining whether AuNP-triggered physical or catalytic events can overcome local buffering and propagate into durable injury. During radiotherapy, AuNPs increase local secondary electron release and ROS formation, which can intensify DNA damage when GSH-dependent peroxide detoxification, thioredoxin-related buffering, and KEAP1-NRF2-regulated antioxidant responses are insufficient to contain the redox burden. In catalytic systems, Au-containing nanozymes can convert endogenous H₂O₂ into highly reactive radicals and may simultaneously deplete glutathione, thereby amplifying mitochondrial dysfunction and lipid peroxidation. During photoactivation, plasmonic heating and photosensitizer coupling further reshape ROS generation in a time-dependent and location-dependent manner. On the diagnostic side, CT or spectral CT can quantify tumor gold burden and coverage, whereas ROS-responsive photoacoustic, SERS, or fluorescence probes can report treatment-related oxidants and verify whether redox activation has occurred within the tumor. Clinical translation will therefore depend on quantification-guided dosing, definition of spatial coverage and activation timing, standardized redox-response readouts, and long-term safety evaluation.