title: Nanoscale Coordination Polymers Codeliver Carboplatin and Gemcitabine for Highly Effective Treatment of Platinum-Resistant Ovarian Cancer.
abstract: Due to the ability of ovarian cancer (OCa) to acquire drug resistance, it has been difficult to develop efficient and safe chemotherapy for OCa. Here, we examined the therapeutic use of a new self-assembled core-shell nanoscale coordination polymer nanoparticle (NCP-Carbo/GMP) that delivers high loadings of carboplatin (28.0 ± 2.6 wt %) and gemcitabine monophosphate (8.6 ± 1.5 wt %). A strong synergistic effect was observed between carboplatin and gemcitabine against platinum-resistant OCa cells, SKOV-3 and A2780/CDPP, in vitro. The coadministration of carboplatin and gemcitabine in the NCP led to prolonged blood circulation half-life (11.8 ± 4.8 h) and improved tumor uptake of the drugs (10.2 ± 4.4% ID/g at 24 h), resulting in 71% regression and 80% growth inhibition of SKOV-3 and A2780/CDDP tumors, respectively. Our findings demonstrate that NCP particles provide great potential for the codelivery of multiple chemotherapeutics for treating drug-resistant cancer.
authors.affiliation: Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poon
authors.affiliation: Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology; D016190:Carboplatin / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010984:Platinum / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D011108:Polymers; D003841:Deoxycytidine; D010984:Platinum; D016190:Carboplatin; D000093542:Gemcitabine
keywords: carboplatin; gemcitabine; nanoscale coordination polymers; platinum-resistant ovarian cancer; synergistic effect