Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy

Bobe Petrushev,1,* Sanda Boca,2,* Timea Simon,2 Cristian Berce,3 Ioana Frinc,4 Delia Dima,4 Sonia Selicean,3 Grigore-Aristide Gafencu,3 Alina Tanase,5 Mihnea Zdrenghea,4,6 Adrian Florea,7 Sorina Suarasan,2 Liana Dima,8 Raluca Stanciu,3 Ancuta Jurj,1 Anca Buzoianu,9 Andrei Cucuianu,4,6,&dagger; S...

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Autores principales:	Petrushev B, Boca S, Simon T, Berce C, Frinc I, Dima D, Selicean S, Gafencu GA, Tanase A, Zdrenghea M, Florea A, Suarasan S, Dima L, Stanciu R, Jurj A, Buzoianu A, Cucuianu A, Astilean S, Irimie A, Tomuleasa C, Berindan-Neagoe I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	tyrosin kinase inhibitors gold nanoparticles acute myeloid leukemia Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bf9edf2aaaeb44a892c2ebe398996ae8
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spelling	oai:doaj.org-article:bf9edf2aaaeb44a892c2ebe398996ae82021-12-02T04:23:13ZGold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy1178-2013https://doaj.org/article/bf9edf2aaaeb44a892c2ebe398996ae82016-02-01T00:00:00Zhttps://www.dovepress.com/gold-nanoparticles-enhance-the-effect-of-tyrosine-kinase-inhibitors-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bobe Petrushev,1,* Sanda Boca,2,* Timea Simon,2 Cristian Berce,3 Ioana Frinc,4 Delia Dima,4 Sonia Selicean,3 Grigore-Aristide Gafencu,3 Alina Tanase,5 Mihnea Zdrenghea,4,6 Adrian Florea,7 Sorina Suarasan,2 Liana Dima,8 Raluca Stanciu,3 Ancuta Jurj,1 Anca Buzoianu,9 Andrei Cucuianu,4,6,&dagger; Simion Astilean,2,10 Alexandru Irimie,11,12 Ciprian Tomuleasa,1,4 Ioana Berindan-Neagoe1,131Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, 3Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 4Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, 5Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, 6Department of Hematology, 7Department of Cell and Molecular Biology, 8School of Dentistry, 9Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 10Faculty of Physics, Babes Bolyai University, 11Department of Surgery, Ion Chiricuta Oncology Institute, 12Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 13Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA*These authors contributed equally to this work&dagger;This author passed away in February 2015Background and aims: 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.Materials and 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.Conclusion: The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.Keywords: tyrosine kinase inhibitors, gold nanoparticles, acute myeloid leukemiaPetrushev BBoca SSimon TBerce CFrinc IDima DSelicean SGafencu GATanase AZdrenghea MFlorea ASuarasan SDima LStanciu RJurj ABuzoianu ACucuianu AAstilean SIrimie ATomuleasa CBerindan-Neagoe IDove Medical Pressarticletyrosin kinase inhibitorsgold nanoparticlesacute myeloid leukemiaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 641-660 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	tyrosin kinase inhibitors gold nanoparticles acute myeloid leukemia Medicine (General) R5-920
spellingShingle	tyrosin kinase inhibitors gold nanoparticles acute myeloid leukemia Medicine (General) R5-920 Petrushev B Boca S Simon T Berce C Frinc I Dima D Selicean S Gafencu GA Tanase A Zdrenghea M Florea A Suarasan S Dima L Stanciu R Jurj A Buzoianu A Cucuianu A Astilean S Irimie A Tomuleasa C Berindan-Neagoe I Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
description	Bobe Petrushev,1,* Sanda Boca,2,* Timea Simon,2 Cristian Berce,3 Ioana Frinc,4 Delia Dima,4 Sonia Selicean,3 Grigore-Aristide Gafencu,3 Alina Tanase,5 Mihnea Zdrenghea,4,6 Adrian Florea,7 Sorina Suarasan,2 Liana Dima,8 Raluca Stanciu,3 Ancuta Jurj,1 Anca Buzoianu,9 Andrei Cucuianu,4,6,&dagger; Simion Astilean,2,10 Alexandru Irimie,11,12 Ciprian Tomuleasa,1,4 Ioana Berindan-Neagoe1,131Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, 3Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 4Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, 5Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, 6Department of Hematology, 7Department of Cell and Molecular Biology, 8School of Dentistry, 9Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 10Faculty of Physics, Babes Bolyai University, 11Department of Surgery, Ion Chiricuta Oncology Institute, 12Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 13Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA*These authors contributed equally to this work&dagger;This author passed away in February 2015Background and aims: 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.Materials and 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.Conclusion: The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.Keywords: tyrosine kinase inhibitors, gold nanoparticles, acute myeloid leukemia
format	article
author	Petrushev B Boca S Simon T Berce C Frinc I Dima D Selicean S Gafencu GA Tanase A Zdrenghea M Florea A Suarasan S Dima L Stanciu R Jurj A Buzoianu A Cucuianu A Astilean S Irimie A Tomuleasa C Berindan-Neagoe I
author_facet	Petrushev B Boca S Simon T Berce C Frinc I Dima D Selicean S Gafencu GA Tanase A Zdrenghea M Florea A Suarasan S Dima L Stanciu R Jurj A Buzoianu A Cucuianu A Astilean S Irimie A Tomuleasa C Berindan-Neagoe I
author_sort	Petrushev B
title	Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
title_short	Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
title_full	Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
title_fullStr	Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
title_full_unstemmed	Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
title_sort	gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/bf9edf2aaaeb44a892c2ebe398996ae8
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Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy

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