title: Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines.
abstract: Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure - stellate cells - simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.
authors.affiliation: Department of Food Engineeing, Faculty of Engineering and Architecture, Ahi Evran University, Kırşehir, Turkey. Electronic address: serapyalcin1982@gmail.com.
authors.forename: Serap
authors.initials: S
authors.lastname: Yalçin
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; Department of Surgery, Koç University School of Medicine, Istanbul, Turkey.
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey.
authors.forename: Gözde
authors.initials: G
authors.lastname: Ünsoy
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey.
authors.forename: Maryam
authors.initials: M
authors.lastname: Parsian
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Gündüz
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism; D002460:Cell Line; D050091:Dendrimers / Q000008:administration & dosage* / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D058185:Magnetite Nanoparticles; C104700:PAMAM Starburst; D003841:Deoxycytidine; D014212:Tretinoin; D000093542:Gemcitabine
keywords: Gemcitabine; Nanoparticle; PAMAM dendrimer; Pancreatic cancer; Retinoic acid; Stellate cell lines