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,† 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†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 leukemi

Opportunities and challenges for spintronics in the microelectronics industry

Spintronic devices exploit the spin, as well as the charge, of electrons and could bring new capabilities to the microelectronics industry. However, in order for spintronic devices to meet the ever-increasing demands of the industry, innovation in terms of materials, processes and circuits are required. Here, we review recent developments in spintronics that could soon have an impact on the microelectronics and information technology industry. We highlight and explore four key areas: magnetic memories, magnetic sensors, radio-frequency and microwave devices, and logic and non-Boolean devices. We also discuss the challenges—at both the device and the system level—that need be addressed in order to integrate spintronic materials and functionalities into mainstream microelectronic platforms