Fink Group

Advanced Particles

Logo
University of Fribourg
Department of Chemistry
Chemin du Musée 9
1700 Fribourg
Switzerland
+41 (0)26 300 87 86
+41 (0)26 300 97 39

Current openings

07 Feb 2013
Currently, there are no open positions.

Latest news

22 Apr 2013
Vera Hirsch's work is selected as the cover picture of Nanoscale. more
07 Feb 2013
Calum Kinnear's work is selected as the cover picture of the research section in Angewandte Chemie. more

ResearchApplications & Risks

Applications and potential risks of nanotechnology

Nanoscience is often referred to as “horizontal”, since it can pervade virtually all technological sectors. It brings together different areas of science and benefits from an interdisciplinary or “converging” approach and is expected to lead to innovations that can contribute towards addressing many of the problems facing today's society. Several nanotechnology-based products have been marketed including electronic components, scratch-free paint, sports equipment, wrinkle- and stain-resistant fabrics, sun creams, and medical products.

The launch of products incorporating nanotech is showing clear differentiation across sectors. In general, manufacturing and materials applications like composites and coatings are launching first, electronics and IT applications like advanced memory chips and displays are launching later, and healthcare and life sciences applications like nanostructured medical devices and nanotherapeutics have the longest time-to-market. Acceptance and integration of nanotechnologies particularly in nanomedicine will be a challenge for a number of reasons. Not only do they have to be approved by the regulatory agencies, but also their manufacturing may require significant technological and cultural adjustments on the part of the producers.

In several projects, we concentrate on the use of inorganic particles for a variety of applications. In parallel, by obtaining a thorough understanding of the particle behaviour in cell culture and later in in vivo experiments, we try to essentially evaluate the potential risks of the investigated particles. Apart from fundamental scientific questions, we are also concerned with the development of a methodology to answer questions related to safety and health for present and future users of nanomaterials. Needless to say, all these projects and efforts are carried out by a multidisciplinary team and much collaboration.

Current Projects

Introduction

Many investigations have addressed the toxicity issues associated with different nanoparticles in vitro and in vivo. Studies focus on the influence of size, solubility, surface charge/modification on the biocompatibility of nanoparticles and their use in biological applications. However, the effects of nanoparticle properties on the immune system are still being explored, and studies of many nanoparticle preparations generally fall into two categories: (a) responses to nanoparticles that are specifically modified to stimulate the immune system or (b) undesirable side-effects of nanoparticles.

Currently, two projects focus on nanotoxicology and risk issues in the larger sense.

Risks & Chances

Rapidly increasing research is being conducted to develop novel biomedical nanoparticles for diagnostic and therapeutic applications. The respiratory tract potentially represents an attractive target organ for the aerosol delivery of biocompatible nanocarriers, due to its accessibility and large surface area. Immune reactions, inflammatory responses, and effects of biomedical NPs on the alveolo-capillary barrier, however, are insufficiently characterised to date, despite an important body of epidemiological and experimental research that has addressed toxicological aspects of ambient NP. Dendritic cells (DCs) form a tightly enmeshed network in the entire respiratory tract, occupying a sentinel function by continuously sampling incoming inhaled matter. DCs scrutinise inhaled antigen, inducing innate immunity and/or regulating subsequent adaptive T cell responses.

Results: Uptake of polymer coated magnetic nanoparticles by monocyte-derived DCs (MDDC) was detected by a dose-dependent increase in fluorescence by FACS that was attenuated by concomitant LPS exposure though a maturation effect on MDDC. Intracellular particles were identified by confocal and electron microscopy, and did nor affect expression of surface markers (CD80, CD83, CD86, myeloid DC, or plasmocytoid DC markers) as measured by FACS. Particle exposed MDDC decreased antigen-specific (tetanus toxoid) proliferation in an in vitro autologous CD4+ T cell assay.

Collaboration

  • Dr. med. C. von Garnier - Respiratory Medicine, Berne University Hospital, CH-3010 Berne, Switzerland.

Project

Swiss National Science Foundation (320030-122355) - “Pulmonary immune responses to biomedical nanoparticles and therapeutical applications”.

Risks & Health

In collaboration with various laboratories at EPFL, SUVA (non-profit insurance company under Swiss public law), SECO (State Secretariat for Economic Affairs), the Institute for Work and Health (Institut universitaire romand de Santé au Travail), and medical services a methodology and procedure helping to answer questions related to safety and health for present and future users of nanomaterials was developed. This was initated by EPFL group of chemical and physical safety. A practical, ‘user-friendly’ procedure for internal safety and health management on nanomaterials use consisting was established. The main ‘users’ of this safety and health methodology are researchers who can rapidly assess the (precautionary) hazard class of their activity and consequently apply adequate safety and health measures. In addition, more detailed analyses of the specific activities can be undertaken by safety and health experts when needed and if sufficient data are available. More details soon!

Head

  • MER Dr. T. Meyer - Head of chemical and physical safety, Ecole Polytechnique Fédéral Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Diagnostic Systems

Based on the clinical unmet needs and recent research in biomarkers on Rheumatoid Arthritis (RA) and Osteoarthritis (OA) the main objective of the project is to develop a nanotechnology based novel diagnostic tool for easy and early detection of biomarkers in inflammatory diseases especially RA and OA by using modified SPIONs for (A) bioassay (ex vivo application) and (B) MRI (in vivo detection). A new technology based on multiple functionalized single nanoparticles specifically entering/attaching to cells, to enzymes in serous fluids or organelles in living cells will be used to detect, separate and identify low abundance biomarkers. Newly identified biomarkers will be used to decorate SPION with binding moieties which are specific to the biomarker(s) and can be used diagnostically such as in contrast agents (MRI). A sensitive micro-immunoassay will be developed for special use of these particles in biochemical tests for arthritis. This project is driven by the high clinical need to identify early arthritis and then segment RA and OA patients into progressors/responders or non-progressors/-responders to various treatment options. Inflammatory disorders like RA inducing the destruction of cartilage in 1 % of the population which is accompanied by significant pain, morbidity and mortality leads to reduced capacity to work. OA, a degenerative arthritis is the leading cause of disability among the elderly population. As there is no cure for RA and finally the replacement of e.g. the knee in OA, early diagnostic tools for the detection of the disease progression and the ability to evaluate the efficacy of therapeutic interventions are necessary u.a. for drug development. Existing diagnostic methods often do not permit an early definite diagnosis, so new nanoparticle based diagnostic techniques targeting to the detection of molecular events (based on MRI) with higher sensitivity/specificity will be developed to satisfy the urgent need. More details soon!

Project

FP7-LARGE - “Development of novel nanotechnology based diagnostic systems for Rheumatoid Arthritis and Osteoarthritis” (NanoDiaRA).

Former Projects

Drug/Gene Delivery

In the past we have been involved in the development of magnetic nanoparticles for drug and/or gene delivery in the course of several projects.

Polymer coated superparamagnetic iron oxide nanoparticles (LINK) were successfully administered intra- and periarticularly in studies (24h to 5 days) to the carpal and stifle joint in a sheep model.

Sheep with magnet 1 Sheep with magnet 2
Sheep with extracorporal magnet sutured to the skin of the carpal and stifle joint after surgery.

Three hours after application, the particles were internalised in the synovial membrane without overt tissue reaction, such as inflammatory changes. The biocompatibility within and in the immediate environment of the articular structures was excellent, not or only during a short time and very local inflammation was observed. Though animals were allowed to roam freely, no particles were seen in the chondrocytes and the articular surface remained intact. Systemic elimination occurred in the liver, kidney and to a lesser extent in the lung, where particles were removed from the circulation by macrophages and/or eliminated by filtration in the kidneys. No systemic or tissue-specific inflammatory reactions during the clearing process were encountered and particles were evenly distributed in the tissues. Influence of the magnets could be demonstrated such that migration of the particles towards the magnetic source could be observed.

Collaboration

  • Prof. Dr. med. vet. Brigitte von Rechenberg - MSRU, Equine Hospital, Vetsuisse Faculty, University Zurich, CH-8057 Zurich, Switzerland.
  • Prof. Dr.-Ing. Heinrich Hofmann - Ecole Polytechnique Fédéral Lausanne (EPFL), Powder Technology Laboratory Materials Science and Engineering, CH-1015 Lausanne, Switzerland.

Project

Magnanomed (EU-5th framework) - “Magnetic Nanoparticles for Medical and Biological Diagnostics and Devices”.

Drug/Gene Delivery

Differently coated particles were extensively characterized and tested for magnetically enhanced transfection. We aimed to enhance transfection efficiency by use of novel shorter DNA fragments (PCR products) instead of plasmids, for enhanced green fluorescent protein (EGFP) gene delivery and the application of a pulsating magnetic field.

Stained cells
When presence of iron oxide particles was confirmed with Pearl's Prussian Blue staining, they were most commonly observed in the superficial layers of the synovial membrane (arrows) at all time periods. This section was taken from the lateral aspect of a left stifle 24 h after injection with plasmid-linked- SPION's containing genes encoding for a red fluorescent protein (dsRED).

Our results show that the transfection rates achieved with the magnetic nanoparticles were significantly higher than those achieved with conventional transfection methods. High transfection rates with SPIONs were also achieved with novel PCR products containing only the gene of interest and hence being safer for clinical use.

Collaboration

  • Prof. Dr. M. Hottiger - Institute of Veterinary Biochemistry and Molecular Biology, University Zurich, CH-8057 Zurich, Switzerland.
  • Prof. Dr. med. vet. Brigitte von Rechenberg - MSRU, Equine Hospital, Vetsuisse Faculty, University Zurich, CH-8057 Zurich, Switzerland.

Project

Vetsuisse - “Superparamagnetic iron oxide (SPION) nanoparticles for plasmid and protein delivery in vitro and in vivo: a feasibility study”.

Magnetic Resonance Imaging

Magnetic nanoparticles have been successfully used for magnetic resonance imaging (MRI) of atherosclerotic plaques. Endocytosis into monocytes/macrophages has been proposed as the mechanism for SPION uptake, but a specific receptor has not been identified yet. A potential candidate is the versatile integrin Mac-1 (CD11b/ CD18, αMβ2), which is involved in leukocyte adhesion, complement activation and phagocytosis. In this study, we showed that this integrin Mac-1 is directly involved in particle binding/uptake.

Optical Microscopy 1 Optical Microscopy 1
Corresponding pictures of light microscopy (left) and immunohistochemistry of monocytes identified by an anti-CD14 antibody (right).

Thus, monocytes abundantly expressing Mac-1 and especially activated monocytes expressing activated Mac-1 may be useful vehicles for high resolution MRI labelling of atherosclerotic plaques.

Collaboration

  • Dr. med C. von zur Muehlen - Department of Cardiology & Angiology, University Hospital of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

Mesoporous silica particles

Mesoporous silica (MS) sub-micron particles loaded (10 % w/w) with superparamagnetic iron oxide nanoparticles were produced by a gel-emulsion method in a W/O miniemulsion. They were thoroughly characterised and their interaction with the model anti-cancer drug paclitaxel was investigated both through experiment and simulation.

SEM
SEM micrograph of composite SPION-silica particles.

The differential free adsorption enthalpy of the drug on the porous surface was measured and the influence of pore sizes on it was calculated. Simulation and experiment show that the paclitaxel molecules are adsorbed inside pores larger than 1.6 nm and have a tendency to remain trapped there. These particles are promising for applications such as separation, purification and immobilisation of small molecules of interest, thanks to their high specific surface area, their well defined pore structure and their magnetic properties.

Collaboration

  • Prof. Dr.-Ing. Heinrich Hofmann - Ecole Polytechnique Fédéral Lausanne (EPFL), Powder Technology Laboratory Materials Science and Engineering, CH-1015 Lausanne, Switzerland.