title: Gemcitabine Conjugated Chitosan and Double Antibodies (Abc-GC-Gemcitabine Nanoparticles) Enhanced Cytoplasmic Uptake of Gemcitabine and Inhibit Proliferation and Metastasis In Human SW1990 Pancreatic Cancer Cells.
abstract: BACKGROUND Pancreatic cancer is considered a chemoresistant neoplasm with extremely dismal prognosis and gemcitabine treatment is associated with many side effects and poor overall survival. The study aimed at developing a new nanobioconjugate, which specifically delivered gemcitabine and anti-EGFR antibody into pancreatic cancer cells. MATERIAL AND METHODS The novel nanodrug is based on chitosan platform, which is non-toxic, biocompatibility and biodegradable. We measured the effects of proliferation and metastasis on SW1990 by CCK-8 assay, colony formation assay, wound healing assay and Transwell assay. The expression of related proteins were evaluated by Western blot. RESULTS We synthesized Abc-GC-gemcitabine nanoparticles successfully with the encapsulation rate of nanobioconjugates was 91.63% and the drug loadings was 9.97%. Both GC-gemcitabine microspheres solution (GC group) and Abc-GC-gemcitabine microspheres solution (Abc group) inhibited cells proliferation, colony formation, migration and invasion in SW1990 cells dramatically. Moreover, Abc-GC-gemcitabine microspheres expressed more significant inhibited action than GC-gemcitabine microspheres efficiently CONCLUSIONS Our data suggested that Abc-GC-gemcitabine nanoparticles could have promising potential in treating metastasized and chemoresistant pancreatic cancer by enhancing the drug efficacy and minimizing off target effects.
authors.affiliation: Department of Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang, China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang, China (mainland).
authors.forename: Haibo
authors.initials: H
authors.lastname: Yu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D048271:Chitosan; D000093542:Gemcitabine