Abstract
Light is an attractive trigger for release of active molecules from nanocarriers in biological systems. Here, we describe a phenomenon of light-induced release of a fluorescent dye from lipid nano-droplets under visible light conditions. Using auto-emulsification process we prepared nanoemulsion droplets of 32nm size encapsulating the hydrophobic analogue of Nile Red, NR668. While these nano-droplets cannot spontaneously enter the cells on the time scale of hours, after illumination for 30s under the microscope at the wavelength of NR668 absorption (535nm), the dye showed fast accumulation inside the cells. The same phenomenon was observed in zebrafish, where nano-droplets initially staining the blood circulation were released into endothelial cells and tissues after illumination. Fluorescence correlation spectroscopy revealed that laser illumination at relatively low power (60mW/cm2) could trigger the release of the dye into recipient media, such as 10% serum or blank lipid nanocarriers. The photo-release can be inhibited by deoxygenation with sodium sulfite, suggesting that at least in part the release could be related to a photochemical process involving oxygen, though a photo-thermal effect could also take place. Finally, we showed that illumination of NR668 can provoke the release into the cells of another highly hydrophobic dye co-encapsulated into the lipid nanocarriers. These results suggest dye-loaded lipid nano-droplets as a prospective platform for preparation of light-triggered nanocarriers of active molecules.
Highlights
Triggered release of active molecules from nanocarriers has been a subject of intensive research in the last decades [1,2,3,4,5,6]
Solutol® (Kolliphor®) HS 15 / Labrafac® WL nanoemulsions loaded with hydrophobic Nile Red derivative NR668 was incubated with cells and studied by wide-field fluorescence microscopy
Earlier works showed that its parent analogue Nile Red could spontaneously internalize [58], which implies that plasma membrane is not really a barrier for these hydrophobic dyes
Summary
Triggered release of active molecules from nanocarriers has been a subject of intensive research in the last decades [1,2,3,4,5,6]. The other approach utilizes surface plasmon and photo-thermal effects, to trigger the cargo release In this case, most commonly gold nanoparticles, nano-rods or nano-shells, are used in combination with polymer, lipid nanocarrier or thermo-sensitive covalent bonds [24,25,26,27,28]. In order to develop organic photo-responsive systems one should use dyes encapsulated inside a nanocarrier In this case, dyes operate as photosensitizers generating highly reactive singlet oxygen and/or as converters of light energy into heat. The use of organic dyes as triggers of molecular release from a nanocarrier were mainly realized in lipid vesicles, where local photothermal or photochemical effects were proposed as driving mechanisms of photo-release [38,39,40,41,42]. The light-driven release of coencapsulated molecule (second encapsulated dye) along with the Nile Red derivative was validated, which proposes the route to light-controlled drug release from lipid nano-droplets
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