Projects / Programmes
Developement of multifunctional hybrid liposomes for active cancer treatment and multimodal diagnostics
| Code |
Science |
Field |
Subfield |
| 2.04.00 |
Engineering sciences and technologies |
Materials science and technology |
|
| Code |
Science |
Field |
| T152 |
Technological sciences |
Composite materials |
| Code |
Science |
Field |
| 2.10 |
Engineering and Technology |
Nano-technology |
liposomes, magnetic nanoparticles, photo-thermal therapy, magnetic resonance imaging, active targeting, cancer, drug delivery
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
35589 |
PhD Nina Kostevšek |
Materials science and technology |
Head |
2018 - 2020 |
114 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
90,742 |
Abstract
This proposal addresses new concepts in cancer treatment and diagnostics based on a single multi-functional nanosystem. The proposed liposomal system will enable a selective targeting of the cancer cells via binding to the epidermal growth factor receptor (EGFR), the remotely-triggered drug release and the multi-functional diagnostics (magnetic resonance imaging and fluorescence imaging). To realize this, the innovative liposomal system will contain five active components:
1. temperature-responsive liposomes will enable remote drug release and prolonged retention time in the body
2. cytotoxic drug (doxorubicin) in the core of the liposomes will be remotely activated
3. magnetic nanoparticles in the lipid bilayer play a dual role; heating actuators for remotely-triggered drug release and the contrast agent for magnetic resonance imaging,
4. near-infrared dye in the core of the liposomes with the dual role; an imaging agent for the fluorescence imaging and for the enhancement of the efficacy of the photo-thermal therapy
5. targeting ligand (monoclonal anti-EGFR antibodies) on the surface of the liposomes for the active targeting of the cancer cells
Such multifunctional liposomes represent an elegant and effective solution to the shortcomings of the existing conventional chemotherapy and diagnostics. The project is organized sequentially towards the final goal – the development of a preclinical proof-of-concept-efficient theranostic system. In the first part of the project, the focus will be on the synthesis optimization and ex vitro evaluation of the performance of each active component separately before constructing the final hybrid system. In the second part of the project, in vitro testing on normal urothelial cells, semi-differentiated and a fully differentiated urothelial cancer cells will be performed to evaluate the biocompatibility and the cellular uptake of the hybrid liposomes, which, due to the active targeting with monoclonal antibodies, is expected to be the highest by the cancerous cells while the uptake by the normal cells should be minimal. Then, the in vitro fluorescence imaging and MRI on all three cell lines with different designs of hybrid liposomes will be performed to proof unambiguously that a clear distinction between the normal and cancer cells can be achieved. Finally, the selective treatment of cancerous cells and remotely-triggered drug release from hybrid liposomes will be demonstrated using photo-thermal experiments.
The project proposal follows specific recommendations in nanomedicine research recently issued by the European Commission, which can be found in the report “Roadmaps in nanomedicine towards 2020” and the latest "Strategic Research and Innovation Agenda for Nanomedicine 2016-2030". As can be clearly seen from these documents, the development of new and more effective anti-cancer therapies combined with the advanced diagnostics is crucial to preserve and improve the quality of life. Development of as-proposed "smart" nanomedicine system will represent the cutting edge technology, thereby increasing the technological innovation level of Slovenia and Europe as it being the major competitive factor in the medical market. Furthermore, the hybrid system proposed in this project is not limited only to the aforementioned applications. With the modification of individual active components, this hybrid system can be used to treat several diseases where an effective drug transfer and a controlled release is required.
Significance for science
The project proposal follows specific recommendations in nanomedicine research recently issued by the European Commission, which can be found in the report “Roadmaps in nanomedicine towards 2020” and the latest "Strategic Research and Innovation Agenda for Nanomedicine 2016-2030". As can be clearly seen from these documents, the development of new and more effective anti-cancer therapies combined with the advanced diagnostics is crucial to preserve and improve the quality of life. Development of as-proposed "smart" nanomedicine system will represent the cutting edge technology, thereby increasing the technological innovation level of Slovenia and Europe as it being the major competitive factor in the medical market. Furthermore, the hybrid system proposed in this project is not limited only to the aforementioned applications. With the modification of individual active components, this hybrid system can be used to treat several diseases where an effective drug transfer and a controlled release is required. In particular, I would like to point out its potential use for the treatment of the neurodegenerative diseases, which in addition to cancer are currently one of the major issues of an aging population. Current issues with the treatment of the neurodegenerative diseases are associated with the drug transfer over the blood-brain barrier (BBB). In our project, urothelial cells that form the only denser barrier in the human body that is the BBB will be used. Successful demonstration on urothelial cell lines that the multifunctional hybrid liposomes are highly selective, safe and efficient theranostic system will open up also new options for the treatment of the neurodegenerative diseases. Furthermore, one of the main objectives of the project is the development of far more efficient contrast agents for MRI than the currently existing ones on the market. Therefore, with the successful outcome of this project, a research breakthrough in the field of diagnostics is inevitable.
Significance for the country
The project proposal follows specific recommendations in nanomedicine research recently issued by the European Commission, which can be found in the report “Roadmaps in nanomedicine towards 2020” and the latest "Strategic Research and Innovation Agenda for Nanomedicine 2016-2030". As can be clearly seen from these documents, the development of new and more effective anti-cancer therapies combined with the advanced diagnostics is crucial to preserve and improve the quality of life. Development of as-proposed "smart" nanomedicine system will represent the cutting edge technology, thereby increasing the technological innovation level of Slovenia and Europe as it being the major competitive factor in the medical market. Furthermore, the hybrid system proposed in this project is not limited only to the aforementioned applications. With the modification of individual active components, this hybrid system can be used to treat several diseases where an effective drug transfer and a controlled release is required. In particular, I would like to point out its potential use for the treatment of the neurodegenerative diseases, which in addition to cancer are currently one of the major issues of an aging population. Current issues with the treatment of the neurodegenerative diseases are associated with the drug transfer over the blood-brain barrier (BBB). In our project, urothelial cells that form the only denser barrier in the human body that is the BBB will be used. Successful demonstration on urothelial cell lines that the multifunctional hybrid liposomes are highly selective, safe and efficient theranostic system will open up also new options for the treatment of the neurodegenerative diseases. Furthermore, one of the main objectives of the project is the development of far more efficient contrast agents for MRI than the currently existing ones on the market. Therefore, with the successful outcome of this project, a research breakthrough in the field of diagnostics is inevitable.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
