Probiotic Spore-Based Oral Drug Delivery System for Enhancing Pancreatic Cancer Chemotherapy by Gut–Pancreas-Axis-Guided Delivery

The chemotherapeutic effectiveness of pancreatic ductal adenocarcinoma (PDAC) is severely hampered by insufficient intratumoral delivery of antitumor drugs. Here, we demonstrate that enhanced pancreatic cancer chemotherapy can be achieved by probiotic spore-based oral drug delivery system via gut–pancreas axis translocation. Clostridium butyricum spores resistant to harsh external stress are extracted as drug carriers, which are further covalently conjugated with gemcitabine-loaded mesoporous silicon nanoparticles (MGEM). The spore-based oral drug delivery system (SPORE-MGEM) migrates upstream into pancreatic tumors from the gut, which increases intratumoral drug accumulation by ∼3-fold compared with MGEM. In two orthotopic PDAC mice models, tumor growth is markedly suppressed by SPORE-MGEM without obvious side effects. Leveraging the biological contact of the gut–pancreas axis, this probiotic spore-based oral drug delivery system reveals a new avenue for enhancing PDAC chemotherapy.