Projects / Programmes
Analiza fukcionalizacije ter mobilnosti magnetnih nanodelcev in vitro za uporabo v biomedicinskih aplikacijah (Slovene)
| Code |
Science |
Field |
Subfield |
| 2.21.00 |
Engineering sciences and technologies |
Technology driven physics |
|
| Code |
Science |
Field |
| 2.10 |
Engineering and Technology |
Nano-technology |
Researchers (9)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
19411 |
PhD Vladimir Boštjan Bregar |
Materials science and technology |
Head |
2009 - 2012 |
105 |
| 2. |
28664 |
PhD Boštjan Drnovšek |
Electric devices |
Junior researcher |
2009 |
10 |
| 3. |
22280 |
PhD Aljoša Košak |
Materials science and technology |
Researcher |
2009 |
207 |
| 4. |
24724 |
PhD Branka Mušič |
Civil engineering |
Researcher |
2012 |
119 |
| 5. |
19225 |
PhD Mojca Pavlin |
Systems and cybernetics |
Researcher |
2010 - 2012 |
262 |
| 6. |
30724 |
PhD Sara Prijič |
Neurobiology |
Junior researcher |
2009 - 2011 |
22 |
| 7. |
34460 |
Maruša Stražišar |
Biochemistry and molecular biology |
Researcher |
2011 - 2012 |
6 |
| 8. |
29375 |
PhD Vid Šuštar |
Biochemistry and molecular biology |
Researcher |
2011 |
75 |
| 9. |
10019 |
PhD Andrej Žnidaršič |
Electronic components and technologies |
Researcher |
2010 - 2011 |
206 |
Organisations (1)
Significance for science
Characterization of NPs in biologically relevant media is crucial for nanotoxicology as well as for development of nanobiotechnological and biomedical applications. The main scopes of this project were the development of a method for characterization of NPs in biological conditions, understanding mechanisms of NP aggregation in biologically relevant media and analysis of interactions of NPs with biological systems. Base on the knowledge on synthesis, functionalization and characterization of NPs acquired during this project we designed functionalized multimodal MNP suitable for visualization, drug delivery and specific targeting. Proper characterization and better understanding NP interactions with biological systems enables the development of NP based biomedical applications.
First we established protocols for preparation of stable suspensions of different MNP cores, which were than functionalized with different biocompatible macromolecules and other substances (DNA, fluorescent dies …). Using our magnetic measuring systems we showed the importance of NP microstructures and primary aggregates on the magnetic state of the system, which is important when using such NP for magnetic hyperthermia.
By using measurement systems for MNP characterization we extended our understanding of interactions between MNP and organic macromolecules and determined how different parameters (ion concentrations, pH) affect their stability in biologically relevant media. We showed that the presence of proteins and divalent ions in the media can cause destabilization. This stresses the importance of characterization in biologically relevant media for NP used for biomedical purposes. By understanding the mechanisms of destabilization we can also predict the effects of certain media on NP stability and behaviour, therefore our publication of mechanisms of destabilization in biologically relevant media should be interesting for wider nanobiomedical field.
We also developed a 3D in vitro model, which in combination with a numerical model enables to assess the mobility of different MNP in gels when exposed to different external magnetic fields. This system will be also used for experiment involving magnetic guiding of MNPs in in vitro and in vivo systems.
The developed protocols for multilayer functionalization of MNPs enabled us to design nanosystems, optimized for different for applications like drug delivery, labelling and visualization, some of which were already used in collaboration with other research groups. Using fluorescence microscopy, scanning (SEM) and transmission electron microscopy (TEM) we determined the degree of aggregation, mechanisms of internalization and intracellular fate of our MNPs. Using SEM we also showed the first steps of internalization: MNPs associated with different membrane protrusions typical for macropinocytosis and clathrin mediated endocytosis. This enabled us to determine the dynamics of internalization, quantification and cytotoxicity, which opens new research possibilities in field of nanotoxicology.
Developed magnetic nanoparticles and protocols are a platform for various specific applications as they allow multimodal behaviour, e.g. visualization with NMR or fluorescence and drug intake. In addition, further functionalization for release of bound active drugs or macromolecules witin the cells, e.g. in the lysosome.
We also developed special multilayer MNP, suitable for delivery of nucleic acids into the cells, with which we improved the magnetofection protocols with the collaboration of the research group from Institute of Oncology Ljubljana. These stable functionalized MNPs form complexes with plasmids caring therapeutic or reporter genes and in this way enable their delivery in the cytoplasm using external magnetic fields.
Significance for the country
This is an interdisciplinary project and covers the fields of nanotechnology, technics, biomedicine and biotechnology. Nanoparticles currently represent one of the most perspective methods in biotechnological and biomedical applications, especially for targeted drug delivery. Interdisciplinarity of the group, covering the fields of magnetic materials, composites, numerical modeling, experimental methods for characterization of NP and in vitro experiments enables us to integrate our experimental work with theoretical analysis through all steps of NP development, including the numerical modeling using the finite element method.
Development of new biomedical applications – transfer of the new technologies into clinical testing:
In collaboration with research groups specializing in transfer of nanotechnological products into biomedical applications we have developed new types of specially functionalized MNP and provide professional support in the fields of magnetism and magnetic materials and characterization of surface functionalized materials, in this was contributing to introduction of these new biomedical techniques also in Slovenia. Based on our acquired knowledge, we established collaborations with Institute for Cell Biology (Faculty of Medicine, UL) and Faculty of Electrical Engineering (UL) and a successful collaboration with Institute of Oncology Ljubljana for the development of NPs for cancer immuno-gene therapy based on magnetofection (paper published in A’’ category, Slovenian patent).
Development and transfer of new technologies:
During this project we developed and established new technologies for characterization of MNP in Slovenia and developed several functionalization protocols. In collaboration with other research groups we developed new protocols for visualization of internalization of NPs in cells using fluorescent and electron microscopy. We also determined NP toxicity and are developing a method for quantification of NP internalization. International award in nanotoxicology opened up possibility of wider integration with partners within the EU in the field of nanotoxicology and nanobiotechnology.
Development of new products and transfer to industry:
We successfully build new knowledge in the field of nanomaterials for biotechnical and biomedical applications for the purpose of connecting research groups and the final transfer of developed NPs to the industry or in the clinical use. With acquired knowledge on characterization and development of NPs we will develop NPs for specific applications (patents) and possibly also connect with the industry (international patent application for NPs as a method of cell visualization).
Transfer of advanced numerical models in biotechnology:
We successfully developed a 3D numerical model for evaluating mobility of NP in gels and in tissues. This enables us to optimize functionalization of new NPs and develop external magnetic systems for biomedical applications in vivo.
Connecting high-tech knowledge with education system:
The project leader and the collaborating partners have experience with work in interdisciplinary groups and were mentors to several graduate and doctoral students in various fields, from electrical engineering to biology and medicine, the acquired knowledge is also transmitted to students through lectures at the interdisciplinary doctoral program Biosciences, field of Nanosciences (UL). Five doctoral students were involved with the project in various steps of development and experimentation. Involvement with the project enabled them to try and learn new high-tech nanotechnological and biomedical methods.
Most important scientific results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
