title: Drug conjugated nanoparticles activated by cancer cell specific mRNA.
abstract: We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Gossai
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Naumann
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Zamora
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.|Department of Chemistry, University of Chicago, Chicago, IL, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA.|University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Gordon
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D000069439:Dasatinib / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006046:Gold / Q000008:administration & dosage / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012333:RNA, Messenger; D006046:Gold; D000069439:Dasatinib
keywords: anti-sense; drug delivery; gold nanoparticles; leukemia; molecularly targeted therapy