Novel drug-free cascaded nanoparticles induce tumor-specific ROS storms via multimodal synergistic anticancer therapy

), further exacerbating oxidative stress within the tumor microenvironment. Transcriptomic analysis revealed that ROS and TNF signaling pathways represented key mechanisms underlying tumor elimination by this multimodal synergistic strategy. Real-time PCR analysis and ELISA assays further validated activation of the TNF signaling pathway. Importantly, this study first confirmed the high biocompatibility and biosafety of HGMP NPs via serum metabolomics, demonstrating no detectable systemic metabolic perturbations. Collectively, the prepared HGMP NPs provide a rational paradigm for synergistic anticancer therapy. These findings highlight the potential of HGMP NPs as an exceptionally safe and effective nanoplatform for cancer treatment, offering valuable insights into future developments in cancer nanomedicine.