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.

Figure 1. Liposome delivery and measurement system.

(A) Dopamine was encapsulated within the liposome's bimolecular lipid membrane. Hollow gold nanoshells (HGN) were tethered to the membrane. Femtosecond laser pulse train induces dopamine release from the liposome structures. (B) The released dopamine was measured using fast scan cyclic voltammetry. Triangular voltage pulses were applied to the carbon fiber electrode at 10 Hz. The current response to the voltage pulse showed an oxidation and reduction peak at the respective potentials of dopamine. (C) The UV/visible/NIR spectra of HGN.

Figure 2. Pulsatile, repeatable dopamine release.

(A) Rapid increase in dopamine concentration stimulated by a one-second laser exposure followed by a decrease due to diffusion process. (Inset) Pulsatile release by repeated one-second laser exposures over 100 s of seconds. (B) We observe an initial rapid, and then slow decrease in dopamine released per exposure after multiple laser exposures. This dynamic can be fitted by bi-exponential curve and is explained by assuming two populations of liposomes with different delivery mechanisms.

Figure 3. On-demand, repeatable and sub-second drug delivery.

We demonstrate repeated dopamine pulses with arbitrary concentration and temporal profiles controlled via the laser intensity and exposure time respectively. The insets show the linear rise in dopamine concentration during laser exposure, with faster dopamine release rates for higher laser intensities and more prolonged release with longer pulses.

Figure 4. The electron microscopy images of liposomes attached to carbon fiber.

(A) Carbon fiber to which liposome structures were fixed for repeated measurement. Rectangle denotes the zoomed in region in (B) before liposome were attached, (C) after liposomes were attached and (D) after laser exposure. One observes a large number of speckles in (C) indicating the attached liposomes and a slightly reduced number in (D) due to losses after laser exposure. A few nominal circles and squares are guides for the eye, with circles as examples of regions where liposomes attach and remain attached after laser exposure (robust population). Squares are examples of regions where liposomes attach but are destroyed after laser exposure (fragile population).