Fig. 1

Scheme of homoeostatic restoration of pancreatic desmoplastic stroma. a Schematic diagram of the fabrication of the ATRA and HSP47 siRNA co-delivery system based on pH-responsive gold nanoparticles. Anionic ATRA and siRNA were electrostatic absorbed onto “sheddable” PEG-grafted polyethylenimine (PEI)-coated gold nanoparticles. b Schematic diagram of PSCs re-education and stroma modulation by the nanosystem. The nanosystem is “activated” (PEG shedding, size decrease, charge increase, and hydrophobic ligand exposure) in the acidic pancreatic tumour microenvironment (pHe ~6.5) and exhibits pHe and ATRA dual-enhanced cellular uptake and HSP47 knockdown in PSCs. Consequently, activated PSCs revert to quiescent phenotype and the desmoplastic stroma is homoeostatically restored, with improved blood perfusion and drug delivery