Light-Responsive Molecular Release from Cubosomes Using Swell-Squeeze Lattice Control

Abstract

Stimuli-responsive materials are crucial to advance controlled delivery systems for drugs and catalysts. Lyotropic liquid crystals (LLCs) have well-defined internal structures suitable to entrap small molecules and can be broken up into low-viscosity dispersions, aiding their application as delivery systems. In this work, we demonstrate the first example of light-responsive cubic LLC dispersions, or cubosomes, using photoswitchable amphiphiles to enable external control over the LLC structure and subsequent on-demand release of entrapped guest molecules. Azobenzene photosurfactants (AzoPS), containing a neutral tetraethylene glycol head group and azobenzene-alkyl tail, are combined (from 10−30 wt %) into monoolein-water systems to create LLC phases. Homogenization of the bulk LLC forms dispersions of particles, ∼200 nm in diameter with internal bicontinuous primitive cubic phases, as seen using small-angle X-ray scattering and cryo-transmission electron microscopy. Notably, increasing the AzoPS concentration leads to swelling of the cubic lattice, offering a method to tune the internal nanoscale structure. Upon UV irradiation, AzoPS within the cubosomes isomerizes within seconds, which in turn leads to squeezing of the cubic lattice and a decrease in the lattice parameter. This squeeze mechanism was successfully harnessed to enable phototriggerable release of trapped Nile Red guest molecules from the cubosome structure in minutes. The ability to control the internal structure of LLC dispersions using light, and the dramatic effect this has on the retention of entrapped molecules, suggests that these systems may have huge potential for the next-generation of nanodelivery.

Multiple Routes to Bicontinuous Cubic Liquid Crystal Phases Discovered by High‐Throughput Self‐Assembly Screening of Multi‐Tail Lipidoids

“…However, few studies explicitly describe nanostructured liquid crystalline particles produced by fully synthetic amphiphiles. [1,70,71] Here, we developed a straightforward protocol to prepare colloidally-stable cubosomes of protonated lipidoid LCs (Figure 6A).…”

Multiple Routes to Bicontinuous Cubic Liquid Crystal Phases Discovered by High-Throughput Self-Assembly Screening of Multi-Tail Lipidoids

“…LNPs based on natural and synthetic lipid assemblies are now attracting significant attention as gene delivery However, few studies explicitly describe nanostructured liquid crystalline particles produced by fully synthetic amphiphiles. [1,74,75] Here, we developed a straightforward protocol to prepare colloidally-stable cubosomes of protonated lipidoid LCs (Figure 6A).…”

Photoswitchable imines: aryliminopyrazoles quantitatively convert to long-lived Z-isomers with visible light

“…Molecular photoswitches, molecules that can reversibly switch between two or more states in response to light, are frequently used in the construction of light-responsive materials [1][2][3][4][5][6][7][8] and the operation of functional molecular machines. [9][10][11][12][13] In nature, the photoinduced E/Z isomerisation of a cis C]C bond in retinal to the trans conformation is fundamental in the mechanism of vision, whilst commercial applications of photoswitches include photochromic lenses, energy storage materials, 14,15 and volumetric 3D printers.…”