Boosting pancreatic cancer chemotherapy by disrupting nerve–cancer crosstalk

A preclinical study has developed a precision nano-intervention strategy targeting tumor-associated nerves to destroy nerve-fueled tumor growth in pancreatic cancer. In this strategy, Escherichia coli Nissle 1917-derived outer membrane vesicles (OMVs) are decorated with nerve-binding peptide for targeted delivery of co-loaded tropomyosin receptor kinase (Trk) inhibitors to tumor-associated nerves, thus precisely inhibiting nerve activity through the neurotrophin/Trk signaling pathway. Furthermore, the OMVs trigger M2-M1 switching, thus accelerating nerve injury. This nano-intervention strategy significantly enhances chemotherapy efficacy in pancreatic cancer.