title: Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy.
abstract: OBJECTIVE
  Every year, in Europe, acute myeloid leukemia (AML) is diagnosed in thousands of adults. For most subtypes of AML, the backbone of treatment was introduced nearly 40 years ago as a combination of cytosine arabinoside with an anthracycline. This therapy is still the worldwide standard of care. Two-thirds of patients achieve complete remission, although most of them ultimately relapse. Since the FLT3 mutation is the most frequent, it serves as a key molecular target for tyrosine kinase inhibitors (TKIs) that inhibit FLT3 kinase. In this study, we report the conjugation of TKIs onto spherical gold nanoparticles.
  
  
  METHODS
  The internalization of TKI-nanocarriers was proved by the strongly scattered light from gold nanoparticles and was correlated with the results obtained by transmission electron microscopy and dark-field microscopy. The therapeutic effect of the newly designed drugs was investigated by several methods including cell counting assay as well as the MTT assay.
  
  
  RESULTS
  We report the newly described bioconjugates to be superior when compared with the drug alone, with data confirmed by state-of-the-art analyses of internalization, cell biology, gene analysis for FLT3-IDT gene, and Western blotting to assess degradation of the FLT3 protein.
  
  
  CONCLUSIONS
  The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Bobe
authors.initials: B
authors.lastname: Petrushev
authors.affiliation: Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, Cluj-Napoca, Romania.
authors.forename: Sanda
authors.initials: S
authors.lastname: Boca
authors.affiliation: Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, Cluj-Napoca, Romania.
authors.forename: Timea
authors.initials: T
authors.lastname: Simon
authors.affiliation: Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Berce
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Frinc
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Delia
authors.initials: D
authors.lastname: Dima
authors.affiliation: Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Sonia
authors.initials: S
authors.lastname: Selicean
authors.affiliation: Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Grigore-Aristide
authors.initials: GA
authors.lastname: Gafencu
authors.affiliation: Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Tanase
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Mihnea
authors.initials: M
authors.lastname: Zdrenghea
authors.affiliation: Department of Cell and Molecular Biology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Florea
authors.affiliation: Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, Cluj-Napoca, Romania.
authors.forename: Sorina
authors.initials: S
authors.lastname: Suarasan
authors.affiliation: School of Dentistry, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Liana
authors.initials: L
authors.lastname: Dima
authors.affiliation: Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Raluca
authors.initials: R
authors.lastname: Stanciu
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ancuta
authors.initials: A
authors.lastname: Jurj
authors.affiliation: Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Buzoianu
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Andrei
authors.initials: A
authors.lastname: Cucuianu
authors.affiliation: Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, Cluj-Napoca, Romania; Faculty of Physics, Babes Bolyai University, Cluj-Napoca, Romania.
authors.forename: Simion
authors.initials: S
authors.lastname: Astilean
authors.affiliation: Department of Surgery, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Irimie
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D006046:Gold; D051941:fms-Like Tyrosine Kinase 3
keywords: acute myeloid leukemia; gold nanoparticles; tyrosine kinase inhibitors