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New nanomaterials for magnetic hyperthermia

#G-2282


Development and study of new nanomaterials for magnetic hyperthermia of cancer cells

Tech Area / Field

  • MAT-SYN/Materials Synthesis and Processing/Materials
  • PHY-OPL/Optics and Lasers/Physics
  • PHY-SSP/Solid State Physics/Physics

Status
3 Approved without Funding

Registration date
10.02.2016

Leading Institute
Georgian Technical University, Georgia, Tbilisi

Supporting institutes

  • Institute for Physical Research, Armenia, Ashtarak-2

Collaborators

  • UCLA School of Medicine/Department of Neurology, USA, CA, Los-Angeles\nCEO/MaxInno Ltd, Denmark, Aarhus\nLaser Zentrum Hannover e.v., Germany, Hannover\nNational Technical University of Athens, Greece, Athens\nUniversitat Duisburg-Essen, Germany, Essen

Project summary

The Project aim. The goal of the present project is the development, optimization and preliminary (entry-level) testing on mice of novel, high-efficient and minimally invasive nano-sized high capability heat mediators of thermal energy transfer, for magnetic hyperthermia treatment of cancer at the cellular level. The required power of the alternating magnetic field (AMF) and toxicity of used nano-materials is aimed to be as low as possible.

Current status. Magnetic nanoparticles in an alternating magnetic field show significant heating effects due to hysteresis losses during the magnetization reversal process. Magnetic nanoparticle-based (MNP) hyperthermia uses a similar principle, because magnetic nanoparticles are introduced into the tumor tissue producing local heat when subjected to an alternating magnetic field (AMF). In a number of recent appropriate scientific papers different types of MNPs with various shape anisotropy, morphology and magnetic properties have been examined and proposed for magnetic hyperthermia applications. Their performance depends on a wide range of parameters, such as concentration, average size and size distribution (dispersivity), type of magnetic hysteresis, saturation magnetization, as well as on amplitude and frequency of the applied AMF [1-3]. The magnetic moment of iron oxide nanoparticles may be increased due to doping of magnetite with metal ions, such as manganese, cobalt and nickel [4]. In addition, r2 relaxivity increases proportionally to the diameter of the magnetic core [5]. These factors have recently been used to create magnetic nanoparticles with significantly higher relaxivity for applications of MR diagnostics [6]. It is generally accepted that the temperature of exposure to the agent should be within 42−44ºC (in some papers, 41-43ºC), as lower temperatures do not provide the desired therapeutic effect, whereas higher temperature causes irreparable damage to healthy tissues [7-12]. Obviously, maintaining of temperature in this range is a nontrivial task and requires precise control of the field parameters, accurate measurement of the temperature of exposure and tissue at the point of impact, as well as other parameters of the whole process (mass transfer, heat supply, etc.). That is why the search and exploration of new magnetic materials, methods of control of the applied AMF and temperature of heating agents and exposed areas, as well as precise setting of the basic parameters of the process and their visualization, becomes so important. Thus, magnetic nanoparticles with temperature of ferromagnetic–paramagnetic phase transition (Curie temperature TC) in the range of about 42−44 o C are of particular interest, because they can be used as media for self-regulated (“negative feedback”) magnetic hyperthermia [13]. Such particles can provide a local self-regulated heating of cancer cells by AMF, without damaging the healthy (not diseased) tissues, since at temperature above TC magnetic nanoparticles become paramagnetic and are not heated by the external electromagnetic field. At temperature below TC as a result of paramagnetic-ferromagnetic transition nanoparticles are again heated by AMF and thereby, the affecting temperature is kept in the relatively narrow range, contributing to the aimed therapeutic effect and avoiding any significant damaging of the healthy tissues. Obviously, for biomedical applications, these nanoparticles should be nas low-toxic as possible) materials and/or they must be sufficiently coated with any inert substances harmless to healthy cells [14].

The project’ influence on progress in this area. The main aim is to synthesize magnetic nanoparticles having high specific absorption rates (SAR) and provide the needed surface functionalization, which can be effectively used to measure the thermal effects along with varying the magnetic field strength and frequency. Using solid-phase pyrolysis of metalorganic precursors, we propose to synthesis carbon encapsulated nanoparticles of iron, magnetite and their nanoalloys with different concentration of compounds. Synthesis of iron and iron oxide nanoparticle in iron-phthalocyanine matrix is also proposed. Advantages of these methods are simplicity, high efficiency and purity of the obtained product, environmental safety of the process. Carbon coated Ni-Cu nanoalloys with TC = 42-44 o C will be synthesized and tested as a material for self-regulating magnetic hyperthermia. Recently, the nanostructured La1-xAgxMnO3 has attracted great attention for magnetic hyperthermia applications. The recently obtained nanomaterial with very specific properties is also proposed as a basis for magnetic hyperthermia with precisely regulated and controlled Tc (in a wide temperature range. Comparison of toxicity of Ni-Cu and La1-xAgxMnO3, as well as decrease of producing time, increasing the yield of synthesis and accuracy of reproducibility of materials with given parameters will be also important for the progress in this area of research. As is known, doping of ferrites with manganese increases the magnetic features which can also be significant target for research. The microwave enhanced synthesis will be also applied for producing iron, magnetite and their nano-alloys with different concentration, and carbon coated Ni-Cu nanoalloys. At the same time, the optimal methods of synthesis of La1-xAgxMnO3 will be identified and applied. All materials will be studied and compared and conclusion on the advantages (or disadvantages) of applied methods will be made. Preliminary testing of developed materials on mice will provide the required data for determining and comparison of therapeutic efficiency and toxicity of developed materials.

The participants’ expertise. All experimental works will be carried out by highly qualified specialists, having more than 30-year experience in materials science, physics and chemistry of micro- and nano-dispersive media, high-power microwave systems, spectroscopy, microscopy, materials science, application of hi-tech equipment for synthesis and investigation of nanocomposites. The microwave enhanced processes will be studied using appropriate advanced and specially designed microwave resonators and reactors. Preliminary (entry-level) testing of developed materials on mice will be carried out by highly qualified and experienced researchers working in the appropriate fields of medicine, toxicology and physiology. All main participants of the project have long-term experience in the field of synthesis and complex structural and magnetic investigations of magnetic nanoparticles and nanoalloys in different biocompatible organic matrix. Competence and qualification of the key participants in the specified areas are confirmed by the list of references given in the detailed project information.

Expected results and their application. It is expected to prepare novel magnetic materials in different biocompatible organic matrix for magnetic hyperthermia treatment of cancer cells.


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