Projects / Programmes
Impact of inorganic nanoparticles on biological membranes
| Code |
Science |
Field |
Subfield |
| 1.03.00 |
Natural sciences and mathematics |
Biology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 1.06 |
Natural Sciences |
Biological sciences |
magnetic nanoparticles, biological membranes, endothelium, thrombocytes, microvesiculation, blood
Researchers (19)
Organisations (5)
Abstract
Scientific background:
Nanomaterials, naturally occurring or produced by nanotechnologies, are particles less than 100 nm in size in any dimension which, as a result of their small size exhibit novel properties. The use of nanotechnology products in the field of medicine could revolutionize diagnosis of diseases, drug delivery and treatment of diseases. The expectations of nanoparticles in medicine are that they may cause less damage to healthy cells and allow for earlier detection of diseased cells than conventional methods. The expectation of nanotechnologies is that they produce particles which will not alter their properties when entering the biological environment and will have targeted action. However, safety issues regarding new products must be addressed as well, while the field is still developing.
Problem description and hypothesis:
In medical applications, it is necessary that nanomaterials be haemocompatibile and non-toxic, and also biodegradable. This is of high importance when substances are administered intravenously what may lead to severe negative side effects as activation of platelets, microvesiculation of different cell types, platelet aggregation, and vascular thrombosis. Our hypothesis is that nanoparticles interact first with biological membranes what subsequently provoking a cascade of cellular events. The type and intensity of integrations depend on agglomeration state of NPs. These events are substantially different in healthy individuals versus cancer patients.
Aim:
The aim of our study is to assess whether the agglomeration state is among more important characteristics of NPs which direct their effects in circulatory system. In addition, the study design will allow to confirm whether these interactions differ in blood of healthy individuals and cancer patients.
Materials and methods:
In the proposed project, interactions between nanoparticles and biological membranes will be studied in different experimental systems with artificial lipid membranes and the results will be verified first in vitro on cell cultures and finally on blood samples from healthy and cancer patients. We will focus on those nanoparticles with a potential for intravenous administration like carbon based, ceramic, metal and metal oxide nanoparticles. The particles will vary in primary (size, shape crystal structure) and secondary characteristics (aggregation in biological media, zeta potential) and in the surface chemistry (protein corona, different coatings)
Originality:
The originality of our study lies in consideration of biophysical mechanisms in seeking an understanding of bio-nano interactions and in linking basic molecular and in vitro cell studies with clinical blood samples studies. The blood samples of healthy individuals and cancer patients will be investigated what has not been done before. Latter are the real candidates for intravenous of NPs with diagnostic or cure purposes.
Project team:
The leading team is a partner in two centres of excellence in Slovenia (CO NAMASTE and CO Nanocentre) and a partner in two large-scale integrating EU FP7 project NanoValid and NanoMile as well as a member of NanoSafety cluster. The researchers from University Clinical Centre will be responsible for providing well characterised blood samples. In addition to Slovenian researchers, also two foreign partners will be included in the project. These are Elettra Sincrotrone centre in Trieste (http://www.elettra.trieste.it/about/index.html) and Indian Institute of Toxicology Research (http://www.iitrindia.org/). Partners from Elettra, prof. Maya Kiskinova and dr. Lisa Vaccari are responsible for three different beamlines for x-ray based analyses and FTIR investigation of cell and tissue samples. The partner from Indian Institute of Toxicology Research, prof. Alok Dhawan, has will be responsible for mathematical modelling.
Significance for science
The project generated two important scientific findings. The first one reveals that size of particles and aggregates is not directly related to reactivity and adverse effects of nanoparticles. Reactivity of nanoparticles depends on a combination of several characteristics and is significantly related to molecular corona. Biocorona is a layer of molecules adsorbed to the surface of the particles. Particle uptake into a cell (endocytosis) is also not related to particle size only. The cell can internalise very large particles. We have proven that the particle uptake and their subsequent photoactivation successfully destroy the cells. This fact points to the promising possibilities of using particles for cancer therapy. This finding was recognized as one among 10 best achievements of the University of Ljubljana in 2017 (IMANI, Roghayeh, et al. Multifunctional gadolinium-doped mesoporous TiO2 nanobeads ephotoluminescence, enhanced spin relaxation, and reactive oxygen species photogeneration, beneficial for cancer diagnosis and treatment. Small, 2017, vol. 13, iss. 20, str. 1-11). Another important finding of the project reveals that internalised particles interfered with the formation of laminar bodies and with the metabolism of surfactants (KONONENKO, Veno, et al.. Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells. Nanotoxicology, 2017, vol. 11, no. 3, str. 419-429). These results pointed to new type of nano-related effects on lung cells. The results of the entire project provided new knowledge on interactions between nanomaterials and biological membranes. We confirmed that cells have many mechanisms to mitigate the effects of exposure to nanomaterials where membranes and vesicles have important role. The project also contributed significantly to the development of test methods for hemocompatible studies. At present, there is no internationally recognized methodology for biocompatibility testing for intravenous infusion of nanoparticles. Existing methods for testing the biocompatibility of materials are limited because nanoparticles have unique physicochemical properties and trigger nano-specific interactions with biological components. It is therefore necessary to develop new methods and regulations in this field. In the project, we have shown that nanoparticles provoke changes in erythrocyte shape and cause formation of exosomes. Both responses proved to be a suitable biomarker for detecting the effects of particles on blood cells and thus their biocompatibility.
Significance for the country
1. Due to the active activity in the field of nanoscience and applications of nanomaterials in medicine and in the field of nanotechnology, Prof. Dr. Damjana Drobne was invited to join the delegation of the President of the Republic of Slovenia, Borut Pahor, in Iran, at opening of the Slovenian embassy in Tehran in November 2016. During the visit, a Memorandum of Scientific Cooperation was signed between the Iranian Institute of Nanotechnology (INIC) and the Research Agency of the Republic of Slovenia (ARRS) in the field of nanotechnology and nanosciences. 2. Project leader Prof. Dr. Damjana Drobne co-funded of Slovenian Nanotechnology Platform under the auspices of the Slovenian Innovation Meeting (SIS EGIZ; www.sis-egiz.eu) in June 2017. 3. Prof. dr. Drobne has proposed and is leading a Task Force for TiO2 (https://www.nanosafetycluster.eu/task-forces/proposed-task-forces/proposed-task-force-on-tio2.html) to adequately and accurate cover the scientific findings regarding TiO2 and TiO2 nano safety and to provide independent and transparent scientific opinion and advice to stakeholders. The Task Force will also try to propose a scheme for communicating scientific evidence regarding nanomaterial safety findings in the most efficient and transparent way.
Most important scientific results
Annual report
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
final report
