Objectives of NanoCHEM
The major Project Objectives are:
1) Studies of physical and chemical properties of nanomaterials using micro-spectroscopic methods.
2) Pre-clinical in vitro and in vivo studies of cancer cell/tumor reaction to the nanoparticles based therapy using double nanoparticle-effect: physical (hyperthermia, cavitation, upconversion, singe oxygen generation) after radiowaves, light and ultrasound irradiation and chemotherapeutic (as chemotherapeutics delivery agent).
3) Pre-clinical toxicity, metabolism, accumulation and pharmacokinetics in cell/small animals studies of nanoparticles with defined physical-chemical properties using Raman Spectroscopy, Fluorescence Microscopy and Optoacoustic tomography
4) Setting (developing/ validating) and writing down bioanalytic methods for the quantitative determination of the investigated TKI in AML patients, based on mass spectrometry.
5) Using the MS-based methods for monitoring the plasmatic concentrations in the clinic, with patients who are repeatedly administered the investigated drugs, which from a pharmacokinetic and toxicological point of view justify the therapeutic monitoring, in order to establish the correct medication, to improve efficiency and clinical safety.
6) Training of young investigators in state-of-the-art research in nano-pharmacology, based on the experience of the senior researchers from Romania and Norway.
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 AML 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 AML 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 AML. 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 AML follow-up when treated with TKI
Aim 1a. To identify and validate a new method for AML follow-up after treatment with TKI, based on mass spectrometry.
Aim 1b. Compare the new follow-up method with the current methods used in the clinic
Aim 1c. Assess the in vivo effects of various nano-carriers functionalized with FLT3 inhibitors, on murine models of AML
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.
The application of gold nanoparticle-based and up-converting nanostructures in cancer theranostics is new and challenging. The future development of advanced bio-medical technologies, based on these materials, will benefit from the anticipated gain of preclinical studies of these novel nanostructures. Our interest in the proposed project concerns the toxicology effects of these novel nanostructures, which are currently considered extremely promising systems for the realization of efficient drug delivery agent and antitumor therapy.
The main focus of the project is the design of innovative nanostructures for bio-medical applications, including their use against cancer cells (bio-imaging using optoacoustic tomography, Raman spectroscopy and fluorescence microscopy) and cancer (cell and tumor) therapy with mininal side-effects on the healthy surrounding cells. This project has a five-fold main focuses: (i) nanomaterial synthesis, characterization, photo/chemo-stability studies; (ii) metabolism (cellular uptake) and toxicity (cytotoxicity, genotoxicity, proteomics studies) studies of nanoparticles at (pre)clinical environment; (iii) in vivo/in vitro visualization of nanoparticles in tumor or in cancer models using optoacoustic, fluorescence microscopy and Raman spectroscopy; (iv) pre-clinical (at 2 Romanian cancer centers and using a murine model of AML) implementation of “two-in-one” concept based on double nanoparticle effect, as possible drug delivering (cancer therapeutic) and therapy agent which can adduced to cancer cell apoptosis due to targeting the FLT3 protein; (v) validation of a new MS-based method for the follow-up of patients diagnosed with AML that receive second-line chemotherapy with TKI.