Functionalised magnetic nanoparticles for promotion of WNT signalling activation and neurite outgrowth and migration

Parkinson’s disease (PD) is characterised by the loss of midbrain dopaminergic neurons within the substantia nigra, responsible for dopamine regulation via their projections through the nigrostriatal pathway that connects to the striatum(1). Thus, reconstruction of this crucial pathway is essential for improving cell transplantation therapies for PD. Wnt signalling is an important developmental pathway that regulates dopaminergic cell proliferation and differentiation(2).Here we propose methods to promote and study both neurite out-growth, migration and Wnt activation(3) using magnetic nano-particles in 2D and 3D experimental models to assess magnetic field stimulation as a remote activator.

Magnetic nanoparticles ( MNPs) were functionalised and coated with a peptide, UM206 (which binds to Wnt Frizzled receptors), and used to label the dopaminergic neuronal cell line, SH-SY5Y. An oscillating magnetic field was applied and expression of dopaminergic markers were assessed via immunocytochemistry. MNPs were also coated with graphene-oxide and internalised in cells PC-12 andSH-SY5Y cells, using P21-8R(4), a transfection agent. 3D collagen-based hydrogel models were created and optimised in which neuronal differentiation of graphene-oxide MNP labelled cells was induced during the application of a static magnetic field. Neurite outgrowth and migration was investigated using confocal imaging and immunocytochemistry.

Results indicate that UM206 coated MNPs showed successful activation of Wnt signalling and subsequent increase of dopamine expression markers. The 3D hydrogel systems showed promising potential as useful and relevant models to investigate neuronal migration and outgrowth. The use of MNPs and their functionalisation can be considered encouraging tools in remote control of cellular functions and behaviour.