Projects / Programmes
Tunneling nanotubes for innovative urinary bladder cancer treatments
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
tunneling membrane nanotubes, cancer, bladder, urothelium, biocompatible composite nanoparticles, gene therapy, biomimetic and orthotopic models
Researchers (29)
Organisations (6)
Abstract
Scientific background and problem introduction
Urinary bladder cancer is 6th among all cancers worldwide and 1/3 of urinary bladder cancer emerges as multifocal tumours at different sites of the urothelium, e.g. epithelium which represents effective blood-urine barrier. Treatment usually includes the resection of the tumours during the transurethral resection of the urinary bladder. Despite the progress of surgical and chemotherapeutical approaches, the prognosis is still poor, mostly due to high recurrence rate of these tumours. Moreover, 50% of patients with invasive urinary bladder cancer die within five years from diagnosis. Intercellular communication is essential for tissue development during embryogenesis and growth, for tissue maintenance during adulthood and also for cancer cells survival and tumour development. One of the mechanisms for intercellular communication is long membrane protrusions named tunnelling membrane nanotubes – TnT. In the proposed project we will examine mechanisms that enable the transfer of biocompatible composite nanoparticles and signal molecules by TnT, which will significantly contribute to the understanding of this relatively new form, however widespread intercellular communication. Based on the obtained results, we will develop innovative approaches for the treatment of urinary bladder cancer.
Aims of the project are: 1) analysis of cellular-biological mechanisms of TnT formation, their molecular structure and ultrastructure and also their function in cancer and normal urothelial cells, and 2) development of innovative approach for treatment of urinary bladder cancer combining advanced diagnostics, targeted application, and transfer of anticancer drug. This targeted anticancer therapy will be founded on the use of TnT a) as targets for anticancer drugs, which will inhibit the formation of TnT and b) as a route for transfer of anticancer drugs between cells. For targeted drug delivery and for sustained therapeutic effect, we will develop biocompatible composite nanoparticles and specific fusion gene constructs.
Execution and management of the project:
The project is organized sequentially towards the final goal, i.e. preclinical testing of suggested targeted therapy on biomimetic in vitro models and by orthotopic in vivo models of bladder cancer. The project is divided into the three workpackages and it is presented graphically in the attached file (Graphical Abstract-TnT 2015_angl.pdf). The work on the project will be executed at the laboratories of 7 partners participating in the project. The consortium provides key elements guaranteeing the success of the project, namely, the choice of excellent researchers, complementary expertise and experience, proven track record of previous successful collaborations between partners, and all the necessary equipment available. Besides the scientific work the project leader will be in charge of the technological aspect and will monitor the project, overseeing the implementation of the work on the basis of the results and provide high-quality follow-up of the work packages to the project completion. The management and coordination of the project will be assured by regular meetings and constant communication with partners on the project.
Relevance and potential impact of the results
The main goal of our project is focused on the maintaining and improvement of the quality of life. Project is very ambitiously constructed and aims to move boundaries of knowledge at the field of cell biology with regards to innovative approaches of bladder cancer treatment as well as wider and relevant also for treatment of other cancer diseases, which present one of the biggest health, social, and economical burdens for the society. The chances of the translation of the project results into clinical practice and to the market are high, also because of the active participation of a clinical partner in the project: clinical partner presents the final user and provid
Significance for science
Intercellular communication is essential for the proper function of cells in normal tissue. On the other hand, it has a significant impact on tumor growth and the tumor metastasis capacity and thus the development of secondary tumors throughout the body. Despite intensive research of intercellular communication there are many unresolved issues about entire route of transmission of molecules and cellular compartments from donor to the acceptor cell. In the present project, we intend to examine the mechanisms that enable such transfer of nanodelivery systems and information molecules by the TnT. Because of the ubiquity of these communication structures between cells, their knowledge will significantly contribute to the understanding of this relatively new form of intercellular communication. Knowledge of the mechanisms involved in the transmission via TnT will allow to elaborate methods, which selectively inhibit the formation of these connections between tumor cells. This is expected to decrease/inhibit tumor growth and to prevent the processes which could lead to metastasis.
In vitro models, designed for this purpose, will provide highly controlled micro-environment for cancer and normal urothelial cells. Moreover, they will enable genetic manipulation of cells and at the same time simplicity to follow targeted anticancer drug delivery system. Translation will be accomplished by the development of orthotopic in vivo model of the urinary bladder cancer, with the aim to enhance the relevance of our results.
Development of appropriate delivery systems, which need to be selective for cancer cells, is of great importance for the basic science and for the subsequent application in the clinics. The biggest challenge when preparing appropriate materials for the scientific or technological field is the opportunity of their development. In these cases, knowledge of the synthesis of appropriate materials enables an explosion of research, new products and technologies.
Proposed project is based on the combination and integration of life- and material- sciences. The results of our project will improve the scientific value of all collaborating groups and their worldwide acknowledgements. Great quality of our results will lead to publications in the journals with high impact factors. We will present our results at international symposiums. Our consortium, composed of experts from cell and molecular biology, oncology, pharmacy and nanotechnology, chemistry biochemistry, and histology guarantees for the achievement of new knowledge, diagnostics and treatment strategies for improved cancer management. We expect that the results of our project will lead to the new wave of the top international research, which will highly promote Slovenian science community.
Significance for the country
Bladder cancer represents the largest cost of treatment per patient among all malignancies (Sievert et al. World J Urol. 2009, 27, 295). The high relapse rate and the progression from non-invasive to invasive forms, and requirements for constant invasive patient monitoring contribute to the economic and social burden of the disease. It is estimated that the cost per patient in the event of early stages of bladder cancer, this is a non-invasive cancer, moving around € 7,000 (Svátek et al., European Urology, 66, 253). In most countries around the world and in Slovenia, the incidence and mortality from bladder cancer grow. The enormous economic and psychological burdens due to bladder cancer are factors that highlight the importance of research to improve the diagnostic and treatment methods. Numerous studies are therefore directed to finding new approaches for the treatment of bladder cancer patients. Urologists in Slovenia underline the need for cooperation of various disciplines, such as the only means of enabling improvements (Smrkolj, 2015 Symposium Basic, preclinical and clinical research and cell biology-urology, April 14, 2015, Ljubljana, Slovenia). The chances of the translation of the project results into clinical practice and to the market is importantly increased by the active participation of a clinical partner in the project. Clinical partner presents the final user and provides end user requirenments, which are crucial for development of the successful product.
Although research in the field of medicine are particular the fundamental but the actual use quite remote, it can be acquired knowledge of practical importance in cooperation with the Slovenian pharmaceutical companies. The experience drawn from the research of the proposed project will be the basis for new products that the spin-off company of the Institute Jožef Stefan (Application Scientificae d.o.o.) can directly offer to the Slovenian and international market. The company already markets products in conjunction with functionalized magnetic nanoparticles. The new technologies that would arise as a result of the project, could offer new sophisticated products with greater added value to the market. Since the proposed project is based on the integration and interconnection of experts and research equipment in the field of life and materials sciences, the successfully implemented program of the project work will contribute significantly to improved diagnosis and removal of cancer cells as well as preventing recidivous and spread of cancer. The project results will present new discoveries and new treatment options also for other types of cancer (and not only urothelial), as the direct communication between cells, the research focus of this project, is of crucial importance in vast majority of cancers. As cancer is becoming one of the most important health and socio-economical burdens, the project is of very high relevance.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
