Our research focuses on the study of biodistribution and biological effects of nanoparticles (NPs) released from biodegradable brain implants to evaluate possible health risks. Special emphasis is put on how laser-irradiated NPs interact with brain cells and tissue and how size and shape of the NPs influence the cell-interaction.
Background
Nanotechnology which uses tiny particles about 100 times smaller than a blood cell has an enormous impact on many of the currently emerging medical applications such as diagnosis, drug delivery or for biodegradable implants. Biodegradable NP enriched implants are used for sutureless laser-soldering of blood vessels in the brain. Due to their size, NPs are not recognised by the immune system and can pass the blood brain barrier or the cell membrane to enter almost any cell. The interaction of NPs with cells can cause oxidative stress and/or lead to pro-inflammatory gene expression resulting in brain inflammation or other undesirable brain reaction.
Aim
The main goal of the project is to determine the NP bio-distribution and to quantify and understand possible side-effects. Considering the fact that besides size, shape and material, physiochemical characteristics of the NPs are extremely important, we focus on naïve and laser irradiated NPs imitating the process used for laser-assisted soldering of vascular lesions in the brain. The studies will show how NPs distribute in the body and the blood stream and if they trigger biological reactions, e.g. inflammation in the brain. In a first step, we will produce and carefully characterise a variety of NPs. Secondly, we will study the interaction of NP with cells and brain slices with and without laser irradiation. State-of-the-art optical and electron microscopes will allow us to quantify the internalisation of NPs in cells. Specific fluorescence markers will be used to visualise the production of reactive oxygen species. In a third step we will analyse the mobility and biodistribution of the NP in the brain tissue in vivo i.e. the uptake by the surrounding tissue, the blood and different organs such as liver, spleen, thymus and cervical lymph nodes on a cellular level. Radiotracer encapsulated NPs will allow us to track the NP in the whole body by scintillation counting.
Significance
Our study will gain insight in size-dependent and nano-specific characteristics of cellular uptake of NPs in neuronal cells and brain tissue after release from a biodegradable implant, a field hardly explored and only poorly understood. The results will be made available to the authorities for decision-making with regard to NP regulations.
Original title: Transport of nanoparticles after release from biodegradable implants
Grant: CHF 405'944.-
Duration: 36 months
Project leader
- Prof. Martin Frenz