SN38-Azo1-NPD

**SN38-Azo1-NPD** is a novel, carrier-free, single-molecule hypoxia-activated nanoprodrug designed for enhanced drug delivery and selective activation in hypoxic tumor environments, particularly for **pancreatic cancer**. The nanoprodrug consists of a dimeric prodrug (SN38-Azo1), comprised of two SN38 (the active metabolite of irinotecan and a potent topoisomerase I inhibitor) moieties linked via a self-immolating, hypoxia-sensitive azo-benzene (Ph–NN–Ph) group. SN38-Azo1 molecules self-assemble into nanoparticles (~50 nm) that accumulate in tumors through the enhanced permeability and retention (EPR) effect. In the hypoxic tumor microenvironment where azoreductase enzymes are upregulated, the azo linker is cleaved, releasing active SN38 molecules specifically within the tumor, which dramatically reduces systemic toxicity compared to free SN38. This hypoxia-triggered release provides masked cytotoxicity under normoxic conditions but potent anticancer effects under hypoxic conditions, achieving high drug loading (~80 wt%) and effective tumor suppression in preclinical models[1][4].