Case Study A1: Cluster Tox
Hybrid nanoparticles made up of polymeric and anorganic building blocks and larger clusters assembled thereof are key components in increasingly used and newly developed advanced materials.
Examples of hybrid nanomaterials
Physicochemical properties (e.g. dimension, shape, density of functional groups, surface heterogeneity, dispersity) of nanoparticles influence their interactions with molecules in biologic systems – and therewith their toxicity.
As for the effect those structural parameters of larger, hierarchical hybrid clusters on biological entities, very little is known at the moment. This motivates the research project A1: We want to resolve and understand the role of total size, number of molecules and macromolecular surface functionalisation of hybrid nanoclusters are affecting uptake by and distribution in cells, as well as their stability and toxicity.
Cluster preparation at IPF
At IPF, a modell system of so-called planet-satellite nanostructures will be synthesised.4 The syntesis can be done in a modular fashion, resulting in a library of structurally and compositionally different polymer-linked hybrid nanoparticle clusters.
- The cluster systems will comprise of:
- distinct numbers and sizes of the constituent inorganic nanoparticles and,
- distinct polymer functionalization.
In particular, macromolecular nanoparticle linkers with varying amount of charged functional groups, with pH-responsive groups (mimicking weak polyelectrolytes employed in batteries) and pH-labile groups (mimicking the controlled decay of tumour-targeting clusters at their target site) will be employed.
In-vitro analysis at INM
The cluster systems will be analysed in vitro in a lung model in terms of internalisation, subcellular localisation (confocal laser scanning and dark-field microscopy), lysosomal stability (dye accumulation, lysosomal protein release), and toxicity (cytotoxicity, ROS formation, cytokine release). All experiments involving clusters will be compared with the behaviour of the individual cluster components (i.e. the primary nanoparticles).