After being validated in patient-derived pancreatic cancer cells, the anticancer efficacy is further verified in xenograft mice bearing heterotopic and orthotopic pancreatic tumors, with extended survival and ameliorated systemic toxicity. Transcriptomic profiling reveals perturbed p53, NF- κB, and GnRH signaling pathways interconnected with NOX inhibition.

Moreover, the NDC selectively diminishes non-mitochondrial reactive oxygen species (ROS) but significantly elevates cytotoxic ROS through mitochondrial membrane depolarization. NOX inhibition reprograms the metabolic phenotype by simultaneously impairing mitochondrial respiration and glycolysis. The self-assembled nanoparticle-drug conjugate (NDC) enables hyaluronidase-activatable controlled release and facilitates cellular trafficking. Here, we rationally design diversified cyclodiaryliodonium NADPH oxidase (NOX) inhibitors with tens of nanomolar optimal growth inhibition and implement CD44-targeted delivery using synthesized sulfated glycosaminoglycan derivatives. Pancreatic cancer renders a principal cause of cancer mortalities with a dismal prognosis, lacking sufficiently safe and effective therapeutics.

Is nox safe