Projects / Programmes
Anisotropic magnetic nanoparticles for the magneto-mechanical therapy of cancer
| Code |
Science |
Field |
Subfield |
| 2.04.01 |
Engineering sciences and technologies |
Materials science and technology |
Inorganic nonmetallic materials |
| Code |
Science |
Field |
| T153 |
Technological sciences |
Ceramic materials and powders |
| Code |
Science |
Field |
| 2.10 |
Engineering and Technology |
Nano-technology |
Cancer treatment, bionanomedicine, magnetic nanoparticles, magneto-mechanical effect, in-vitro testing
Researchers (23)
Organisations (3)
Abstract
Methods for cancer treatments that are based on the internalization of nanoparticles in a malignant tissue have already proven to be successful in clinical trials; however, numerous disadvantages have also emerged. Magnetic hyperthermia is based on overheating the malignant tissue, mediated by a relaxation of the nanoparticles’ magnetization in an alternating magnetic field with high frequencies of around 100 kHz. With respect to implementing the method in a health system, a serious obstacle is the high price of a magnetic field applicator that is capable of producing such high-frequency fields. The price of this applicator could be substantially reduced if the treatment were to be effective at lower frequencies. Another important obstacle for the general use of this method is in the way the nanoparticles are introduced into the tumour, which is currently based on direct injection. Alternatively, the nanoparticles could be targeted into tumours after a systemic administration using affinity ligands. However, the problem is with the small quantity of nanoparticles that can be introduced into a tumour using this approach. To be successful, even with these low concentrations of nanoparticles in the tumour, the efficiency of the transfer of the electromagnetic energy to the cancer cells needs to be substantially increased.
In this project we are proposing an entirely new concept for the treatment of cancers based on the transformation of low-frequency magnetic-field energy (1 Hz to 1 kHz) into mechanical energy, mediated by anisotropic magnetic nanoparticles. This mechanical energy will be used to effectively damage the cancer cells. When an anisotropic magnetic nanoparticle is placed in a magnetic field, it is directed in accordance with the applied field. The nanoparticle’s rotation under the influence of the magnetic field results in the transfer of the force to the environment. When the nanoparticle is located at the cell’s surface, or in its interior, the induced force can irreparably damage a cell. In an alternating field a magneto-mechanical resonance is expected, which will then strongly increase the effect. The crucial difference between our approach and conventional hyperthermia is in the much better efficiency of the excitation energy transfer to the cells. As well as for use in therapy, the nanoparticles can also serve for simultaneous diagnostics (theranostics), as they can be detected with magnetic resonance imaging or with magnetic particle imaging.
The rotation of a nanoparticle in a magnetic field can be the consequence of the anisotropy of its magnetic structure (magnetocrystalline anisotropy), or its shape. In this project we will investigate two types of magnetic nanoparticles, where different mechanisms of transfer from the magnetic energy to mechanical energy are expected: (i.) hard-magnetic nanoplatelets (from 50 to 120 nm wide, ~ 5 nm thick), and (ii.) one-dimensional superparamagnetic (SPM) nanochains (300–600 nm long, ~ 90 nm thick).
To test the magneto-mechanical effect, an appropriate magnetic field applicator will be developed. The efficiency of the nanoparticles will be tested in vitro on giant unilamellar vesicles (GUVs) and different cells, including blood cells (erythrocytes), yeast cells, and different types of cancer cells. The experimental research will be supported by theoretical considerations using coupled magneto-mechanical numerical simulations.
The aim of the proposed project is to verify the concept of a completely new cancer therapy. The result of the project will be optimized properties of the excitation magnetic field (i.e., frequency and amplitude) and the magnetic properties and morphology of the nanoparticles capable of transferring magnetic energy to cells with maximum efficiency. However, the planned research will also be very important for understanding the nanoparticles’ interactions with the cells, which is the key issue in nanotoxicology.
Significance for science
The aim of this project is to verify the concept of a completely new cancer therapy based on the magneto-mechanical agitation of anisotropic magnetic nanoparticles internalized into the tumour tissue with an applied AC magnetic field. To the best of our knowledge, the magneto-mechanical effect of the nanoparticles has not yet been studied in relation to its possible applications in medicine. We will study the effect of two types on nanoparticles, two-dimensional hard-magnetic nanoplatelets and 1-dimensional superparamagnetic nanochains, where fundamentally different mechanisms for the transfer of the magnetic energy to the mechanical energy can be expected. The nanoparticles that will be used in the project have a unique morphology and magnetic properties. Their synthesis already enabled some significant scientific breakthroughs, e.g., the magnetic nanoplatelets enabled the preparation of the first magnetic liquid crystals. The magneto-mechanical effect will be tested using original approaches using different biological models. All this gives the project very considerable scientific originality. The project will present new horizons for research on cancer treatment. However, the research related to the basic interactions between the nanoparticles and the cells is generally important, not only for the application of nanoparticles in biomedicine, but also for understanding the possible impact of the produced nanomaterials on health (nanotoxicology). The possibility to transform the magnetic energy to the mechanical energy on the nanoscale using anisotropic magnetic particles may also be important for other technological applications.
The proposed project represents pioneering research with high probability to initiate further research of the magneto-mechanical effects of anisotropic nanoparticles for new applications in physics, electrical engineering, chemical processing technologies, biotechnology and medicine. The experimentalists and theoreticians will find new ideas to investigate new directions for their research activities. Results of the project will be disseminated to international scientific community in form of top-end scientific articles and presentations on domestic and international conferences. Considering actuality of the research (cancer treatment), development of new attractive nanomaterials (composite nanoplatelets, superparamagnetic nanochains), state-of-the-art materials characterization (modern electron microscopy methods, such as STEM-HAADF), interdisciplinary approach in nanomaterials biological testing, and the combination of experiments with theory, publications in the scientific journals with highest impact factor can be expected.
Significance for the country
A large part of the research in the project is directed to the synthesis, functionalization, and characterization of magnetic nanoparticles, nanostructures and nano-suspensions for their use in medicine. The methods that we use for the synthesis of the nanomaterials do not require expensive equipment, as they are based on original scientific approaches and a profound knowledge of the basic chemical processes. The used synthesis methods enable a relatively easy transfer to industrial production. The knowledge developed in the research is thus practically applicable for the development of new technologies, products and services that are important for Slovenian industry. Although the research related to medicine is mainly basic and its applications seem quite distant, the acquired practical knowledge is important in cooperation with Slovenian pharmaceutical companies and SMEs providing specialized services to biomedical research. The cooperation of the Department for Materials Synthesis of Jožef Stefan Institute and the Lek Pharmaceuticals Company on the research related to the development of new nanoparticles-based drugs is already well established. Two spin-out companies of the Department for Materials Synthesis, Nanos Sci. d.o.o. (http://nanos-sci.com/ ) and InoVine d.o.o. (http://www.ino-vine.com/ ), will be indirectly involved in the project. The knowledge obtained in the project can also be a foundation for establishing new companies.
With the progress of nanotechnology an increasing number of different nanomaterials are produced, also in Slovenia, to be used in different technologies. This opens up serious concerns regarding their possible toxicity. The research on the interactions of nanomaterials with biological systems, especially cells, is of enormous importance for an assessment of the nanoparticles’ toxicity (nanotoxicology).
The proposed project will also synergistically contribute to knowledge relevant for other programs and projects, conducted by project partners and others. The knowledge acquired by the project will be disseminated over research, industry, and to society, especially to the Slovenian medical system. In the near future, new methods for diagnostics and treatments based on nanotechnology will be introduced into medical practise. For the introduction of these new methods, the knowledge related to nanomaterials and their interactions with biological systems will be of utmost importance. Results of the project will be disseminated not only to scientific community, but also to general public through popular presentations in mass media and over internet, e.g., at ResearchGate and at home pages of partners’ organizations. Moreover, the gained knowledge will be implemented in educational system, especially at the postgraduate level. (all leading researchers are professors involved at higher educations).
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
