A CXCR4 targeting peptide delivered by silica nanoparticles eliminates migrating cancer stem cells in pancreatic ductal adenocarcinoma - PubMed
5 hours ago
- #Nanoparticle Therapy
- #Cancer Stem Cells
- #Pancreatic Cancer
- The study targets migrating cancer stem cells (miCSCs) in pancreatic ductal adenocarcinoma (PDAC) using a CXCR4-targeting peptide delivered by silica nanoparticles.
- CXCR4 and its ligand CXCL12, secreted by activated pancreatic stellate cells, promote stemness, EMT, and chemoresistance in miCSCs, with BMI1 identified as a key downstream effector.
- Knockdown of CXCR4 or BMI1 impairs miCSC maintenance and migration; the peptide antagonist EPI-X4 and its derivative JM#21 inhibit CXCL12 signaling and reduce EMT/stemness.
- Encapsulating JM#21 in mesoporous silica nanoparticles enhances stability and efficacy, suppressing EMT markers and self-renewal more effectively than the free peptide, and re-sensitizes PDAC cells to chemotherapy.
- Targeting the CXCL12/CXCR4/BMI1 axis with nanoparticle-stabilized JM#21 represents a novel therapeutic strategy to disrupt PDAC progression and improve combination treatment efficacy.