First, ‘RNS-responsive nanocarriers’ – engineered to release payloads (e.g., iNOS inhibitors, NO donors) upon exposure to TME-specific RNS (e.g., ONOO−) or redox cues (e.g., high H2O2) – have shown enhanced tumor accumulation: for example, ONOO−-cleavable polymeric nanoparticles loaded with 1400W (iNOS inhibitor) achieved a 4.2-fold higher tumor-to-normal tissue drug ratio in TNBC xenografts compared to free 1400W, reducing off-target endothelial toxicity [202]. This evidence concerns the gene NOS2 and neoplasm.