Acid-labile boronate-bridged dextran-bortezomib conjugate with up-regulated hypoxic tumor suppression

An acid-labile dextran-bortezomib conjugate (Dex-BTZ), i.e., a macro-molecularized proteasome inhibitor, is synthesized by a boron esterification reaction. The prodrug exhibits intracellular acidity-accelerated BTZ release, and up-regulated inhibition efficacies toward hypoxic tumor in vitro and in vivo through both NF-kappa B- and ERS-mediated apoptosis signaling pathways.