title: Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer.
abstract: Gemcitabine has long been the standard of care for treating pancreatic ductal adenocarcinoma (PDAC), despite its poor pharmacokinetics/dynamics and rapid development of drug resistance. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer-1 (NCP-1) for simultaneous delivery of two chemotherapeutics, oxaliplatin and gemcitabine monophosphate (GMP), at 30 wt.% and 12 wt.% drug loadings, respectively. A strong synergistic therapeutic effect of oxaliplatin and GMP was observed in vitro against AsPc-1 and BxPc-3 pancreatic cancer cells. NCP-1 particles effectively avoid uptake by the mononuclear phagocyte system (MPS) in vivo with a long blood circulation half-life of 10.1 ± 3.3h, and potently inhibit tumor growth when compared to NCP particles carrying oxaliplatin or GMP alone. Our findings demonstrate NCP-1 as a novel nanocarrier for the co-delivery of two chemotherapeutics that have distinctive mechanisms of action to simultaneously disrupt multiple anticancer pathways with maximal therapeutic efficacy and minimal side effects.
authors.affiliation: Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poon
authors.affiliation: Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
authors.forename: Chunbai
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
authors.forename: Demin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA.
authors.forename: Kuangda
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Chemistry, University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA. Electronic address: wenbinlin@uchicago.edu.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D011108:Polymers; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabine; Nanoscale coordination polymers; Oxaliplatin; Pancreatic ductal adenocarcinoma; Synergistic effect