nanofibers inspire novel hypoxic cancer therapy

Carbonic anhydrase (ca) ix enzyme exclusively overexpresses on cell membrane of hypoxic tumors, regulating acidic tumor microenvironment. small molecules of ca inhibitor modified with short peptide successfully achieve ca ix targeted self-assembly that localize ca inhibitors on hypoxic cancer cell surface and enhance their inhibition efficacy and selectivity. besides, ca ix-related endocytosis also promotes selective intracellular uptakes of these nanofibers under hypoxia, by which nanofiber structure upgrades with decreasing ph values. this subsequently cause intracellular acid vesicles damage and protective autophagy blockage. their versatility of tunable nanostructures responding to cell milieu, significantly provoke selective toxicities and provide strategic therapy for hypoxic tumors. moreover, in vivo applications exhibit considerable efficacies of anti-metastasis, and anti-angiogenesis in breast tumor, which has accomplished remarkable enhancements of antitumor efficacies for doxorubicin administration. benefiting from its biocompatible components and distinguished hypoxia therapies, this novel nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy