Using SANS with Contrast-Matched Lipid Bicontinuous Cubic Phases To Determine the Location of Encapsulated Peptides, Proteins, and Other Biomolecules

Abstract

An understanding of the location of peptides, proteins, and other biomolecules within the bicontinuous cubic phase is crucial for understanding and evolving biological and biomedical applications of these hybrid biomolecule-lipid materials, including during in meso crystallization and drug delivery. While theoretical modeling has indicated that proteins and additive lipids might phase separate locally and adopt a preferred location in the cubic phase, this has never been experimentally confirmed. We have demonstrated that perfectly contrast-matched cubic phases in D2O can be studied using small-angle neutron scattering by mixing fully deuterated and hydrogenated lipid at an appropriate ratio. The model transmembrane peptide WALP21 showed no preferential location in the membrane of the diamond cubic phase of phytanoyl monoethanolamide and was not incorporated in the gyroid cubic phase. While deuteration had a small effect on the phase behavior of the cubic phase forming lipids, the changes did not significantly affect our results.

Cubic Liquid Crystalline Nanostructures Involving Catalase and Curcumin: BioSAXS Study and Catalase Peroxidatic Function after Cubosomal Nanoparticle Treatment of Differentiated SH-SY5Y Cells

“…The entrapment of biomolecules of various dimensions and hydrophilicities is achievable in such nanocarriers as well as their sustained release [10,12]. For example, LCPs have been used to encapsulate proteins of different concentrations and sizes from Cyt C (12 kDa) to fibrinogen (340 kDa) [8,11,20,21,22,23,24,25,26,27]. High encapsulation efficacy has been reported for hydrophilic guest macromolecules such as brain-derived neurotrophic factor (BDNF), ovalbulmin and protein vaccines [11,20,21,22,23,24].…”

Inorganic nanoparticles modify the phase behavior and viscoelastic properties of non-lamellar lipid mesophases

“…The presence of additives modifies and controls the geometry of these lipid architectures. This is the case for fatty acids [15,16], photo-switchable molecules [17][18][19], and proteins [20] that can be even crystallized within the lyotropic phase [21,22]. Recently, Briscoe et al [23,24] investigated the effects of hydrophobic silica NPs on dioleoyl-phopshatidylethanolamine mesophases, highlighting a temperature and pressure-dependent lamellar to hexagonal phase transition.…”

Controlling the Kinetics of an Enzymatic Reaction through Enzyme or Substrate Confinement into Lipid Mesophases with Tunable Structural Parameters

“…Due to their unique structure, characterized by the coexistence of extended hydrophobic and hydrophilic regions arranged in a continuous 3D complex architecture, cubic mesophases, in their disperse form, i.e., cubosomes, have been widely studied as possible alternatives to the most common lamellar phases (in particular in their dispersed form, as liposomes) for the development of vectors for drugs of different size and polarity for biomedical applications [ 6 , 10 , 11 , 12 ]. They have been formulated for local and systemic administration, in different routes [ 13 ].…”

“…Compared to liposomes, cubic nanoparticles are characterized by a reduced internal aqueous volume to host hydrophilic drugs; however, their extended membrane surface is particularly suitable for loading of membrane proteins and small drug molecules, as well as hydrophobic molecules [ 14 ]. For instance, they have been employed to transport small hydrophobic molecules as quercetin [ 15 , 16 ] and camptothecin [ 17 ] and photosensitizers [ 18 ], which can be included in the extended hydrophobic regions of cubic mesophases, or hydrophilic or amphiphilic macromolecules and proteins [ 10 , 19 , 20 ], which can be efficiently hosted and retained in the peculiar structure of the aqueous regions, comprising cages and necks. in addition, cubic mesophases have been successfully loaded with hydrophobic or hydrophilic superparamagnetic iron oxide nanoparticles, to build-up smart drug delivery systems, able to release the encapsulated drugs in a spatially and temporally controlled manner [ 21 , 22 ].…”