Supported by a grant from Iceland, Liechtenstein and Norway

Results of NanoCHEM

Two novel preclinical models of AML were generated. Hand-on training for young investigators was carried out. Mobilities for young PhD student in Romania to Norway was done as planned. The therapeutic effect of the newly-designed drugs was investigated by several methods including cell counting assay as well as the MTT assay and was found to be superior when compared with the drug alone, data confirmed by state-of-the art analyses of internalization, cell biology, genomics and proteomics. The obtained results are promising for validating TKI-gold nanocarriers as potential clinical agents for the treatment of acute myeloid leukemia.

Romanian student received high quality training in laboratory research. These students did their dissertation theses, as well as a PhD thesis based on the research funded by this grant: Andra-Sorina Tatar, dissertation thesis, title: “Conjugation of some gold nanoparticles with tyrosine kinase inhibitors and their validation as acute myeloid leukemia therapeutic agents, defense: 02.07.2015, PhD Student Sorina Suarasan, PhD thesis, title: “Gelatin-coated and drug-loaded gold nanoparticles for performing therapeutic and multimodal imaging functionalities, defense: 28.09.2015. The abilities acquired within this common project are: cell culture protocols, flow cytometry, gold nanosctructure bioconjugation with different drugs, biocompatibility assays in vitro and in vivo. Also, abilities in grant management and interpersonal communication and team work have been acquired.

The broader impact is significant, both because new investigators were formed, as well as new therapeutic opportunities emerged for acute leukemia therapy. The work done in this project gave us key insights in the use of nanopharmaceuticals in AML by providing us with key pharmacological parameters such as the minimal effective dose and the toxicological profile of this nanoconstructs, in an experimental setups. These results are the basis for further sustainably developing nanopharmaceuticals in AML, in terms of resources and in a timely fashion for the patients.

Published books
Insights in Hematology - International Congress 1st Edition

Published papers:

1. Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania, March 11-12, 2016. ANCA BOJAN, IOANA BERINDAN-NEAGOE, S. CIUREA, DELIA DIMA, SHIGEO FUJI, G. GHIAUR, RAVNIT GREWAL, EMMET MCCORMACK, ALINA TANASE, A. TRIFA, CIPRIAN TOMULEASA. ROM. J. INTERN. MED., 2016, 54, 3, 157–160.

2. Simon T, Tomuleasa C, Bojan A, Berindan-Neagoe I, Boca S, Astilean S. Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia. Nanoscale Res Lett. 2015; 10(1):466. impact factor: 2.726.

3. Zaharie F, Muresan MS, Petrushev B, Berce C, Gafencu GA, Selicean S, Jurj A, Cojocneanu-Petric R, Lisencu CI, Pop LA, Pileczki V, Eniu D, Muresan MA, Zaharie R, Berindan-Neagoe I, Tomuleasa C, Irimie A. Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer. J Gastrointestin Liver Dis. 2015; 24(4):435-43. impact factor: 2.202.

4. Suarasan S, Simon T, Boca S, Tomuleasa C, Astilean S. Gelatin-coated Gold Nanoparticles as Carriers of FLT3 Inhibitors for Acute Myeloid Leukemia Treatment. Chem Biol Drug Des. 2016; 87(6):927-35. impact factor: 2.802

5. Tanase A, Tomuleasa C, Marculescu A, Bardas A, Colita A, Orban C, Ciurea SO. Haploidentical Donors: Can Faster Transplantation Be Life-Saving for Patients with Advanced Disease? Acta Haematol. 2016;135(4):211-6. impact factor: 0.88.

6. 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. Int J Nanomedicine. 2016; 11:641-60. impact factor: 4.383

7. IN VIVO ASSESSMENT OF BONE MARROW TOXICITY FOR GOLD NANOPARTICLE-BASED BIOCONJUGATES IN CRL:CD1(ICR) MICE. Cristian Berce, Ciprian Lucan, Bobe Petrushev, Sanda Boca, Mirela Miclean, Orsolya Sarpataki, Simion Astilean, Anca Buzoianu, Ciprian Tomuleasa, Anca Bojan. International Journal of Nanomedicine 2016, accepted for publication. impact factor: 4.383