Description
Acute myeloid leukemia (AML) is one of the most common and deadly leukemias worldwide. Its prognosis is poor, in part due to diagnosis at late disease stages. A better understanding of the pharmacological mechanisms underlying acute myeloid leukemia chemotherapy, leading to the development of better early therapeutic tools, are thus imperative. Nanotechnology is emerging as a new and highly promising solution for the management of such cancers and acute myeloid leukemia is a suitable candidate for novel nanotechnology-based diagnostics and therapeutics. Through our ongoing research we have already proven that gold gold nanoparticles are highly efficient DDAs for tyrosine kinase inhibitors (TKI), which represents a premiere in international nano-pharmacology. The previous results obtained by our research group and financed by the EEA grant competition will be continued through the current research proposal in order to obtain high quality data, with great potential to improve the therapeutic ratio of patients diagnosed with acute myeloid leukemia. Moreover, the goal of the research will also be the training of young investigators in highly specific protocols of nanopharmacology and molecular oncology. The following Specific Aims are defined: Aim 1. To identify and validate a new approach in acute myeloid leukemia follow-up when treated with Aim 2. To train young investigators Aim 2a. To complete the training of young investigators and PhD students from Romania (belonging to the Roma minority) and Norway in state-of-the-art techniques in basic and translational cancer research. Training of the young investigators in high technology research protocols, with a special emphasis on the training of young doctors, resident physicians, PhD students and post-doctoral researchers that are of Roma ethnic minority will represent a special feature of the project, in order to help combat discrimination and intolerance.
Summary of project results
The current grant reports hand-on training for young investigators for the the conjugation of TKI-based drug onto spherical gold nanoparticles, their effective trans-membranar delivery inside AML cells and in vitro evaluation as therapeutic against two different AML cell lines: THP1 and OCI-AML3. The efficient formation of drug-nanocarriers was proved by spectroscopic characterization of the particles. The internalization of rituximab-nanocarriers was proved as a result of the strongly scattered light from gold nanoparticles and was correlated with the results obtained by transmission electron microscopy (TEM). The therapeutic effect of the newly-designed drugs was investigated by several methods including cell counting assay as well as the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (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. The donor partnership achieved to bring state-of-the-art research in Romania, as well as support training for very promising researchers in Eastern Europe in Norway. The research carried out ended in opening a new therapeutic window for AML therapy. The target group are now instrumental in the development of future projects such as the further development of AML animal models, generating optimised immunophenotyping and nanopharmaceutical synthesis protocols for acute leukaemias. Apart from the obvious technological transfers which occurred between partners, fruitful work partnerships were establish and this resulted in an improved lab management.
Summary of bilateral results
Together with the Norwegian partner, we managed to receive further funding for moving on to the next level and assessing the toxicology assays for these nanostructures. Hands-on training will be carried on. The data generated in this project proved to be very insightful and will constitute the basis for further advancing our understanding of nanopharmaceuticals and how can we use them in AML, a malady in need of new therapeutic options. A joint meeting was organized in Cluj Napoca in September 2015. Representatives from all institutions were present and gave talks. 80 people attended the meeting and free books were distributed among the participant. Talks were given by Professor Emmet McCormack (University of Bergen), Professor Simion Astilean (Babes Bolyai University), Dr. Anca Bojan, Dr. Cristian Berce and Dr. Ciprian Tomuleasa (Iuliu Hatieganu University). The ppt files of the talk, as well as the list of presence and photographs from the meeting were provided. Free books, written as a result of the collaboration between Romanian and Norwegian partners) were distributed among the participant of the meeting. The role of the University of Bergen was to develop preclinical models of AML and assay nanomedicines produced from Romania in vivo. Furthermore, we facilitated several mobility's to our institution to provide training of younger researchers. Romanian partners developed the technology for the described bioconjugate and regular Skype meeting were held together with the Norwegian partners in order to discuss the data. Thus, hands-on training was carried out. The donor partner contributed highly to the education of young healthcare professionals and researchers in Romania. Training was carried out both in Romania, as well as in Norway, thus forming the backbone for a center of excellence in research in translational hematology and oncology in Cluj Napoca. Apart from supporting the training of young researchers from Romania, the partner also provided the Romanian side with valuable scientific knowledge and support, contributing in a valuable manner to the accomplishments of all the outcomes and outputs. Bilateral partnerships were very much improved between Romania and Norway, as a result of the current project. As a result of this project, as well as other similar projects, international collaboration between the two countries was initiated and future projects, both educational and in research, will be carried out.