title: Nanoscale Coordination Polymers Codeliver Chemotherapeutics and siRNAs to Eradicate Tumors of Cisplatin-Resistant Ovarian Cancer.
abstract: Drug resistance impedes the successful treatment of many types of cancers, especially ovarian cancer (OCa). To counter this problem, we developed novel long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles that efficiently deliver multiple therapeutics with different mechanisms of action to enhance synergistic therapeutic effects. These NCP particles contain high payloads of chemotherapeutics cisplatin or cisplatin plus gemcitabine in the core and pooled siRNAs that target multidrug resistant (MDR) genes in the shell. The NCP particles possess efficient endosomal escape via a novel carbon dioxide release mechanism without compromising the neutral surface charge required for long blood circulation and effectively downregulate MDR gene expression in vivo to enhance chemotherapeutic efficacy by several orders of magnitude. Even at low doses, intraperitoneal injections of nanoparticles led to effective and long-lasting tumor regression/eradication in subcutaneous and intraperitoneal xenograft mouse models of cisplatin-resistant OCa. By silencing MDR genes in tumors, self-assembled core-shell nanoparticles promise a more effective chemotherapeutic treatment for many challenging cancers.
authors.affiliation: Department of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Chunbai
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poon
authors.affiliation: Department of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: S Diane
authors.initials: SD
authors.lastname: Yamada
authors.affiliation: Department of Chemistry, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002245:Carbon Dioxide / Q000097:blood; D002945:Cisplatin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D011992:Endosomes / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering; D002245:Carbon Dioxide; D002945:Cisplatin