On-demand dopamine receptor activation via photoresponsive nanoparticle-dopamine conjugates in differentiated SH-SY5Y and transfected HEK293 cells

Abstract

Parkinson's disease is a complex neurodegenerative disease associated with the reduction of dopamine content in the brain. Dopamine, in the form of the precursor L-DOPA, is used as a replacement therapy, which provides temporary symptomatic relief. Long-term treatment with L-DOPA induces side effects such as involuntary movements (dyskinesia) due to the continuous and non-discriminatory exposure to dopamine. Here, we propose that a reduction in the dose and frequency of administration of L-DOPA might reduce such side effects. We hypothesise that by binding dopamine to a nanoparticle via a photoresponsive moiety, we can not only maintain dopamine's biological activity, but also modulate the availability of dopamine for receptor activation non-invasively through light. To test this hypothesis, we designed a nanoparticle surface functionalised with a photoresponsive spiropyran molecule that is conjugated to dopamine to stimulate activation of the dopamine D₁ receptor (D₁R). The activity of the system was assessed using a cAMP assay on a Parkinson's disease modelled SH-SY5Y neuroblastoma cell line and DRD1/CRE transfected HEK293 cells. We found that cAMP concentration was elevated in treated cells, meaning that the biological activity of conjugated dopamine is maintained and that the dopaminergic receptor is activated on-demand by light stimulation in our model system.