Mimicking subsecond neurotransmitter dynamics with femtosecond laser stimulated nanosystems

Abstract

Existing nanoscale chemical delivery systems target diseased cells over long, sustained periods of time, typically through one-time, destructive triggering. Future directions lie in the development of fast and robust techniques capable of reproducing the pulsatile chemical activity of living organisms, thereby allowing us to mimic biofunctionality. Here, we demonstrate that by applying programmed femtosecond laser pulses to robust, nanoscale liposome structures containing dopamine, we achieve sub-second, controlled release of dopamine – a key neurotransmitter of the central nervous system – thereby replicating its release profile in the brain. The fast delivery system provides a powerful new interface with neural circuits, and to the larger range of biological functions that operate on this short timescale.

Interfacing with Neural Activity via Femtosecond Laser Stimulation of Drug-Encapsulating Liposomal Nanostructures

“…Both mechanisms involve steep temperature gradients that require femtosecond pulse irradiation. Importantly, the present formulation is dominated by the nondestructive process, as evidenced by SEM confirmation of the persistence of liposomal nanostructures before and after light-stimulated release (Nakano et al, 2014). …”

“…D , Liposomes were assembled from components, as described previously. Adapted from the study by Nakano et al (2014) with permission of the authors. Laser spot, Neuronal structures and liposomes not drawn to scale.…”

“…The encapsulation efficiency (∼5.3%) was calculated from the percentage volume within the liposomes compared with the total volume of drug solution used for suspending the lipids. To estimate release, we referred to previous work (Nakano et al, 2014) in which release from liposomes trapped on a carbon fiber was determined by measuring the oxidation current of dopamine. By fitting an exponential curve to a series of release events, the fraction of the cargo released at each event was estimated as 5.8%.…”

“…In previous work, a new method of chemical release from liposomal nanostructures using optical stimulation was described (Wu et al, 2008; Leung and Romanowski, 2012; Nakano et al, 2014; Huang et al, 2015). Liposomal nanostructures are submicron spherical capsules comprising a lipid bilayer shell and an interior space that can be loaded with drugs.…”

“…Liposomal nanostructures are submicron spherical capsules comprising a lipid bilayer shell and an interior space that can be loaded with drugs. By tethering a gold nanoparticle to the liposome wall, the repeatable release of the encapsulated drug from the liposome can be effected by exposure to femtosecond laser pulses (Nakano et al, 2014). By adjusting laser stimulation parameters, the amount and speed of release can be controlled.…”