biostudies-literatureHe XNational Science Fund for Distinguished Young ScholarsFudan-SIMM Joint Research FundNational Natural Science Foundation of China1701070https://www.ebi.ac.uk/biostudies/studies/S-EPMC5979633biostudies-literatureUnknown5(5)Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy with a five year survival rate of <5%. The aberrant expression of extracellular matrix (ECM) in the tumor stroma forms a compact physical barrier, which that leads to insufficient extravasation and penetration of nanosized therapies. To overcome the severe resistance of PDAC to conventional therapies, a sequentially triggered nanoparticle (aptamer/cell-penetrating peptide-camptothecin prodrug, i.e., Apt/CPP-CPTD NPs) with tumor penetration and intelligent drug release profile is designed. An ECM component (tenescin-C) targeting aptamer (GBI-10) is modified onto stroma-permeable cell-penetrating peptide (CPP) for the in vivo CPP camouflage and PDAC-homing. In PDAC stroma, tenascin-C can detach GBI-10 from CPP and expoAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Sequentially Triggered Nanoparticles with Tumor Penetration and Intelligent Drug Release for Pancreatic Cancer Therapy.PMC597963381373355FU-SIMM2017400981425023Chen QLiu LLi CZhang YLu YHe XRuan CSun TJiang CChen XGuo QfalseSequentially Triggered Nanoparticles with Tumor Penetration and Intelligent Drug Release for Pancreatic Cancer Therapy.Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy with a five year survival rate of <5%. The aberrant expression of extracellular matrix (ECM) in the tumor stroma forms a compact physical barrier, which that leads to insufficient extravasation and penetration of nanosized therapies. To overcome the severe resistance of PDAC to conventional therapies, a sequentially triggered nanoparticle (aptamer/cell-penetrating peptide-camptothecin prodrug, i.e., Apt/CPP-CPTD NPs) with tumor penetration and intelligent drug release profile is designed. An ECM component (tenescin-C) targeting aptamer (GBI-10) is modified onto stroma-permeable cell-penetrating peptide (CPP) for the in vivo CPP camouflage and PDAC-homing. In PDAC stroma, tenascin-C can detach GBI-10 from CPP and expo2018-01-01T00:00:00Z2018 May2025-04-26T08:26:36.739Z2019-03-26T23:40:35ZS-EPMC59796332987622510.1002/advs.201701070