Journal
NANO LETTERS
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c03131
Keywords
bacterial translocation; gut-pancreas axis; spores; tumor targeting; PDAC chemotherapy
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Funding
- National Natural Science foundation of China [51988102, 22135005, 51833007]
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The study demonstrates that the probiotic spore-based oral drug delivery system can enhance pancreatic cancer chemotherapy through gut-pancreas axis translocation, increasing drug accumulation within tumors. The system shows significant tumor growth suppression in animal models without obvious side effects.
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 similar to 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.
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